SakmarLab

The Sakmar Laboratory

The Laboratory of
Molecular Biology & Biochemistry
at Rockefeller University

Thomas Haines
Visiting Professor

Laboratory of Molecular Biology and Biochemistry

Rockefeller Research Building 510
The Rockefeller University, Box 187
1230 York Avenue
New York, NY 10065
Telephone: 212-327-8284
Fax: 212-721-9557
thaines@prdi.org

Education:

City College of CUNY - B. S. - 1957
City College of CUNY - M. S. - 1959
Rutgers the State University - Ph. D. - 1964

Research:

Biochemistry, Biophysics, Lipids in Membranes and Cell Biology.
Specific biological roles of membrane lipids: cholesterol, cardiolipin, isoprenes, isopranes, chains of fatty acids (including polyunsaturated), chlorosulfolipids, phospholipid headgroups, & membrane protein/lipid interactions.

Awards:

Visiting Professor
Who’s Who in America, Who’s Who International (2005-pres.)
Chaired Symposium, “Should a Year of Organic Chemistry be Required for Medical School Admission?”, ASBMB/ACS Joint Meeting, San Francisco, CA, (1995).
Biochemistry and Cell Biology Study Section of NIH Institute for Alcoholism and Alcohol Abuse, 1992-95
Twentieth Anniversary Medal, for establishing the CUNY Medical School, (1993).
Honored Professor Award; CUNY Medical School; (1982, 1983, 1986, 1988, 1989, 1992, 1993, 1995).
Member, Association of Graduate and Medical Schools Biochemistry Chairs, (1986-pres.)
Chair, Biophysics Section, New York Academy of Science (1991-1993).
Chair, Symposium on Membrane Dynamics, The biophysical Society, Phoenix, AZ (1988)
Member, American Society of Biological Chemists, Education Committee, (1986-1991)
Member, Medical Advisory Committee, Sophie Davis School for Biomedical Education, Other members included all of the Deans of New York’s Medical Schools. (1974-78).
125th Anniversary Medal, City College of CUNY, (1972).
Elected to the American Society of Biological Chemists (1970).
Chairman; Symposium on Sulfolipids, American Oil Chemists Society, Houston, TX, (1970).
Co-Chairman; Symposium on Lipids and Monolayers, Amer. Oil Chem. Soc., New York, NY, (1970).
Invited by the USSR Academy of Sciences to chair the first symposium on Lipids ever held at a IUPAC Conference; Riga, USSR (1970).
NATO Senior Fellow: Awarded by the National Science Foundation, Paris, France (1970).
NSF-NIH Joint Travel Award to Tokyo, Japan to attend IUB Conference, (1967) (ASBMB Award).
Honors Fellowship, Rutgers the State University (1963).

Books:

Haines, T. H.
(1972) The Sulfolipids. In series: Progress in the Chemistry of Fats and Oils. Series editor, Ralph Holman. Pergamon Press, NY.

Published Papers:

41)
Haines, T. H.
(2009) A new look at cardiolipin.
Biochimica et Biophysica Acta—Biomembranes In Press.

[not indexed on PUBMED]

40)
Bedke, D., Shibuya, G., Pereira, A., Gerwick, W., Haines, T. H., Vanderwal, C.
(2009) Relative stereochemistry determination and synthesis of the major chlorosulfolipid from Ochromonas danica.
Journal of the American Chemical Society, 131, 7570–7572.

PMID: 19445461 [PubMed - indexed for MEDLINE]

39)
Dante, S., Hauß, T., Dencher, N. A. & Haines, T. H.
(2005) Localization of coenzyme Q10 in the center of a deuterated lipid bilayer by neutron diffraction.
Biochimica et Biophysica Acta—Bioenergetics 1710, 57-62.

PMID: 16199002 [PubMed - indexed for MEDLINE]

38)
Haines, T. H. & Dencher, N. A.
(2003) Is cardiolipin a proton trap for ATP synthesis?
FEBS Lett. 528, 35-39. (Includes function of cardiolipin)

[not indexed on PUBMED]

37)
Hauss, T., Dante, S., Dencher, N. A., Haines, T. H.
(2002) Squalene is in the midplane of the lipid bilayer: implications for its function as a proton permeability barrier.
Biochim. Biophys. Acta 1556 149-154.

PMID: 12460672 [PubMed - indexed for MEDLINE]

36)
Mileykovskaya, E., Dowhan, W., Birke, R. L. Zheng, D. & Haines, T. H.
(2001) Cardiolipin binds nonyl acridine orange by aggregating the dye at exposed hydrophobic domains on bilayer surfaces.
FEBS Letters, 507 187-190.

PMID: 11684095 [PubMed - indexed for MEDLINE]

35)
Haines, T. H.
(2001) Do sterols reduce proton and sodium leaks through lipid bilayers?
Progress in Lipid Research, 40, 299-324. (Includes function of cholesterol)

PMID: 11412894 [PubMed - indexed for MEDLINE]

34)
Paula, S., Volkov, A. G., Van Hoek, A. N., Haines, T. H., Deamer, D. W.
(1996) Permeation of Protons, Potassium ions and small polar molecules through phospholipids bilayers as a function of membrane thickness.
Biophys. J. 70 339-48. (Shows H2O permeability is unaffected by chainlength.)

PMID: 8770210 [PubMed - indexed for MEDLINE]

33)
Mas-Oliva, J., Velasco-Loyden, G. & Haines, T. H.
(1996) Receptor pattern formation as a signal for the capture of lipoproteins.
Biochemical and Biophysical Research Communications 224, 212-218.

PMID: 8694814 [PubMed - indexed for MEDLINE]

32)
Haines, T. H. & Liebovitch, L.
(1995) A molecular mechanism for the transport of water across phospholipid bilayers.
In “Permeability and Stability of Lipid Bilayers” S. A. Simon and A. Disalvo, eds. CRC Press, Boca Raton FL. (Includes lateral chain movement vs. H2O permeability of bilayers.)

[not indexed on PUBMED]

31)
Haines, T. H.
(1994) Minireview. Water transport across biological membranes.
FEBS Letters 346, 115-122.

[not indexed on PUBMED]

30)
Kates, M., Syz, J.Y., Gosser, D. & Haines, T.H.
(1993). pH-dissociation characteristics of cardiolipin and its 2'-deoxy analogue.
Lipids 28, 877-882.

PMID: 8246687 [PubMed - indexed for MEDLINE]

29)
Rutkowski, C. R., Williams, L., Cummins, H. Z. & Haines, T. H.
(1992) The elasticity of synthetic phospholipid vesicles obtained by photon correlation spectroscopy.
Biochemistry 31, 5688-96.

PMID: 2043611 [PubMed - indexed for MEDLINE]

28)
Haines, T.H., Li, W., Green, M., & Cummins, H.Z.
(1987). The elasticity of uniform, unilamellar vesicles of acidic.
Biochemistry 26, 5439-5447.

PMID: 3676261 [PubMed - indexed for MEDLINE]

27)
Li, W. & Haines, T.H.
(1986). Uniform preparations of large unilamellar vesicles containing anionic lipids.
Biochemistry 25, 7477-7483.

PMID: 3542028 [PubMed - indexed for MEDLINE]

26)
Li, W., Aurora, T.S., Haines, T.H., & Cummins, H.Z.
(1986). The elasticity of synthetic phospholipid vesicles and. submitochondrial particles during osmotic swelling.
Biochemistry 25, 8220-8229.

PMID: 3814581 [PubMed - indexed for MEDLINE]

25)
Aurora, T.S., Li, W., Cummins, H.Z., & Haines, T.H.
(1985). Preparation and characterization of monodisperse unilamellar phospholipid vesicles with selected diameters from 3000 to 6000 Angstroms.
Biochim. Biophys. Acta 820, 250-258.

PMID: 4052421 [PubMed - indexed for MEDLINE]

24)
Haines, T. H.
(1984) The microbial sulfolipids.
CRC Handbook of Microbiology. Second Edition. Vol. V. A. I. Laskin & H. A. Lechevalier, eds. Boca Raton, FL 115-123.

[not indexed on PUBMED]

23)
Haines, T.H.
(1983). Anionic lipid headgroups as a proton-conducting pathway along the surface of membranes: a hypothesis.
Proc. Natl. Acad. Sci. U. S. A. 80, 160-164.

22)
Haines, T. H.
(1982) A model for transition state dynamics in bilayers. Implications for the role of lipids in biomembrane transport.
Biophys. J. 37, 147-9.

[not indexed on PUBMED]

21)
Haines, T.H.
(1979). A proposal on the function of unsaturated fatty acids and ionic lipids: the role of potential compaction in biological membranes.
J. Theor. Biol. 80, 307-323.

[not indexed on PUBMED]

20)
Chen, L.L., Pousada, M., & Haines, T.H.
(1976). The flagellar membrane of Ochromonas danica. Lipid composition.
J. Biol. Chem. 251, 1835-1842.

[not indexed on PUBMED]

19)
Chen, L.L. & Haines, T.H.
(1976). The flagellar membrane of Ochromonas danica. Isolation and electrophoretic analysis of the flagellar membrane, axonemes, and mastigonemes.
J. Biol. Chem. 251, 1828-1834.

[not indexed on PUBMED]

18)
Haines, T. H.
(1974) The halogenated sulfatides. In, “Biochemistry of Lipids.”
In MTP International Review of Science , Biochemistry Vol. IV, T. W. Goodwin. Ed. Pp.271-286. Butterworths Press, Oxford.

[not indexed on PUBMED]

17)
Haines, T. H.
(1973) Sulfolipids and halosulfolipids.
In, “Lipids and Biomembranes of Eukaryotic Microorganisms.” Ed., J. A. Erwin, Academic Press, NY.

[not indexed on PUBMED]

16)
Mooney, C. L. & Haines, T. H.
(1973) Chlorination and sulfation reactions in the biosynthesis of chlorosulfolipids in Ochromonas danica, in vivo.
Biochemistry 12,4469-72.

[not indexed on PUBMED]

15)
Haines, T.H.
(1973). Halogen- and sulfur-containing lipids in protozoa..
Annu. Rev. Microbiol. 27, 403-411.

[not indexed on PUBMED]

14)
Mooney, C. L., E. M. Mahoney, M. Pousada & Haines, T. H.
(1972) Direct incorporation of fatty acids into the halosulfatides of Ochromonas danica.
Biochemistry 11, 4839-44.

[not indexed on PUBMED]

13)
Aaronson, S., U. Behrens, R. Orner & Haines T. H.
(1971) Ultrastructure of intracellular and extracellular vesicles, membranes and myelin figures produced by Ochromonas danica.
J. Ultrastructure Research 35, 418-30.

[not indexed on PUBMED]

12)
Haines, T. H.
(1970) Algae sulfolipids and chlorosulfolipids.
In, “Properties and Products of Algae.” J. E. Zajic, ed. New York Plenum Press, pp. 129-142.

[not indexed on PUBMED]

11)
Haines, T. H.
(1970) The reduction of alkyl sulfates to alkane with lithium aluminum hydride.
Lipids 5, 149-151.

[not indexed on PUBMED]

10)
Mayers, G.L., Pousada, M., & Haines, T.H.
(1969). Microbial sulfolipids. 3. The disulfate of (+)-1,14-docosanediol in Ochromonas danica.
Biochemistry 8, 2981-2986.

[not indexed on PUBMED]

9)
Haines, T.H., Pousada, M., Stern, B., and Mayers, G.L.
(1969). Microbial sulpholipids. IV. (R)-13-choro-1-(R)-14-docosanediol disulphate and polychlorosulpholipids in Ochromonas danica.
Biochem. J. 113, 565-566.

[not indexed on PUBMED]

8)
Gershengorn, M. C., A. R. H. Smith, G. Goulston, L. J. Goad, T. W. Goodwin & Haines, T. H.
(1968) The sterols of Ochromonas danica and O. malhamensis.
Biochemistry 7, 1698-1708.

[not indexed on PUBMED]

7)
Haines, T. H.
(1967) A new sulfolipid. Application to problems of drug transport. Progr.
In Biochemical Pharmacology, Vol. III, 1848-54

[not indexed on PUBMED]

6)
Mayers, G.L. & Haines, T.H.
(1967). A microbial sulfolipid. II. Structural studies.
Biochemistry 6, 1665-1671.

[not indexed on PUBMED]

5)
Haines, T. H.
(1965) A microbial sulfolipid. I. Isolation and physiological studies.
J. Protozool. 12, 656-659.

[not indexed on PUBMED]

4)
Aaronson, S., B. Bensky, Haines, T. H., J. Gellerman & H. Schlenk.
(1963) Fatty acids of protozoa, especially of phytoflagellates; differences associated with the absence of photosynthetic apparatus in Euglena.
J. Protozool. 10, 9-12.

[not indexed on PUBMED]

3)
Haines, T. H., S. Aaronson, J. Gellerman & H. Schlenk.
(1962) Occurrence of arachidonic acid and related acids in the protozoan, Ochromonas danica.
Nature 194, 1283-4.

[not indexed on PUBMED]

2)
Haines, T. H. & R. Block.
(1962) The sulfur metabolism of algae. I. Synthesis of metabolically inert chloform-soluble sulfate esters by two Chrysomonads and Chlorella pyrenoidosa.
J. Protozool. 9, 33-38.

[not indexed on PUBMED]

1)
Haines, T. H., S. M. Henry & R. Block.
(1960) The sulfur metabolism of insects, V. The ability of insects to use sulfate in the synthesis of methionine.
Contrib. Boyce Thompson Inst. 20, 363-5.

[not indexed on PUBMED]

The Sakmar Laboratory

The Laboratory of
Molecular Biology & Biochemistry
at Rockefeller University

Thomas Huber,
Post Doctoral Associate

Laboratory of Molecular Biology and Biochemistry

Rockefeller Research Building 510
The Rockefeller University, Box 187
1230 York Avenue
New York, NY 10065

Telephone: 212-327-8284
Fax: 212-327-7904

hubert@rockefeller.edu

Curriculum Vitae

Education

Postdoc, Rockefeller University, 2002
Postdoc, University of Arizona, 2002
Postdoc, University of Munich, 2000
Ph.D. in Medicine (Dr. med.), University of Munich , 1999
M.D. (Ärztliche Prüfung), University of Munich, 1995

Teaching Experience
1996–2000 Seminar within the program of preclinical education for medical students covering the entire field of Medical Biochemistry (72 hrs per year), Institute for Physiological Chemistry, University of Munich

Professional membership
Biophysical Society, Bethesda, MD.

Patent application/pending

Rockefeller University, New York, NY
RU 870
A Novel Method for the Production of Nanoscale Membrane Particles
Technology Summary
Inventors
Dr. Thomas Sakmar, Dr. Thomas Huber, and Sourabh Banerjee
Patent Information & References

•Patent pending
•Banerjee, et al. 2008. J. Mol. Biol. DOI: 10.1016/j.jmb.2008.01.066

Research

The goal of my research is to elucidate the biophysical principles of molecular recognition in biomembranes with a special emphasis on transmembrane receptors and their native lipid environment. Despite enormous advances, there are still gaps in scientific understanding of the fundamental processes of molecular biology, such as protein folding, genetic encoding of biomolecular function, and highly selective molecular recognition {Ball, 2006}. In order to address some of these fundamental issues, my strategy is an interdisciplinary approach combining experimental and computational techniques. Keys to this approach are 1) to apply the quantitative measurement process of physical sciences to biochemistry, molecular biology, and pharmacology, and 2) to interpret the molecular mechanism by computer simulations of dynamic models. Currently, my research focuses on the role of the phospholipid membrane in ligand-receptor and protein-protein interactions. The first project addresses the question of how a hydrophobic ligand, 11-cis-retinal, finds its way via the lipid membrane into the buried binding pocket of a seven-transmembrane (7-TM) helix receptor, opsin, a prototypical G-protein-coupled receptor (GPCR). The second project addresses the effect of hydrophobic mismatch on the self-assembly process of receptors in membrane microdomains and resulting changes in receptor function. In the near future, my plan is to miniaturize the experiments employing ultra-sensitive fluorescence microscopy in combination with microfluidics techniques. These nanoscale experiments will enable me, on the one hand, to work with receptors that are difficult to be produced in large quantities and, on the other hand, to switch from ensemble to single molecule measurements. Ideally, the single molecule techniques might reveal completely new mechanistic insight. In a second line of development, I plan to make a stronger connection of the current in vitro approach using reconstituted pure components to in vivo model systems using live cell culture in combination with similar fluorescence microscopy techniques.

Azido labels enable FTIR analysis of rhodopsin activation.
Although recent advances have provided several high-resolution crystal structures of protein-coupled receptors (GPCR), understanding the detailed structural changes upon activation of a GPCR remains paramount. We demonstrate the site-specific incorporation of an infra red (IR)-active unnatural amino acid (UAAM) into the GPCR rhodopsin. We used Fourier transform infra red (FTIR) difference spectroscopy to monitor these amino acids and show specific environmental changes during receptor activation. The conformational changes were consistent with the changes observed in a recent crystal structure, a ligand-free version of rhodopsin. Our long-term goal is to combine an array of experimental and computational biophysical tools to provide a comprehensive model of the activation mechanism of GPCRs. The Sakmar Lab performed the FTIR spectroscopy in collaboration with the Vogel lab at the Albert-Ludwigs-University Freiburg, Germany.

Structural Basis for Ligand Binding and Specificity in Adrenergic Receptors: Implications for GPCR-targeted Drug Discovery.
The crystal structures of beta-2 adrenergic receptors were one of the scientific breakthroughs in 2007. It was the first G protein-coupled receptor (GPCR) with a diffusible ligand, (nor-) epinephrine or adrenaline. In this work, we applied some of the molecular dynamics simulation methodology developed earlier for studies of rhodopsin to this new receptor structure. We were comparing simulations of a "beta-blocker" drug bound receptor with simulations containing the activating hormone adrenaline. Together these simulations exceeded 600 nanoseconds, which render this study computationally as one of the largest simulations in the literature up to that point. These extensive simulations were supported by the National Science Foundation (NSF) that provided generous supercomputing time on the Teragrid nationwide network of massive parallel computer clusters. Huber and are corresponding authors on this paper. Huber serves as the principal investigator of this NSF grant.

Site-specific incorporation of keto amino acids into functional G protein-coupled receptors using unnatural amino acid mutagenesis.
In all living organisms, genetic material (DNA or RNA) is translated into proteins. The genetic code defines a mapping between nucleotide triplets, called codons, and amino acids. Nature utilizes this code to assemble all proteins from only twenty different amino acids, which are the building blocks of proteins. In this work building on results from the Schultz group at Scripps, we have developed a system for unnatural amino acids mutagenesis of proteins in mammalian cell culture, in particular of the two G protein-coupled receptors (GPCRs), visual rhodopsin and CCR5 chemokine receptor. We were able to introduce the unnatural amino acid at an arbitrary, but specific position in the protein. We demonstrated that the receptors were functional, and that the unnatural amino acid could be modified by specific chemical reactions to introduce informative biophysical probes, for example, fluorescence labels. This work was a collaboration of the Sakmar lab and the RajBhandary lab at the Massachusetts Institute of Technology (MIT), Cambridge, MA.

Functional role of the "ionic lock"—an interhelical hydrogen-bond network in family A heptahelical receptors.
The crystal structure of visual rhodopsin from the Palczewski group in 2000 has provided an unprecedented view into the atomic interactions in this prototypical G protein-coupled receptor (GPCR). One of the intriguing observations was the presence of a so called "ionic lock" that appears to keep the receptor in the off state. Here we investigated a series of site-directed mutants of rhodopsin using Fourier transform infra red (FTIR) difference spectroscopy. We were able to quantify the effect of the ionic lock on the on-off equilibrium of the receptor, consistent with the hypothesis. Interestingly, in the recently elucidated structure of beta-2 adrenergic receptor, the ionic lock is broken, and at the same time the off state of this receptor appears to be destabilized. This work was part of a long standing collaboration of the Siebert lab at the Albert-Ludwigs-University Freiburg, Germany, and the Sakmar lab.

Bilateral olfactory sensory input enhances chemotaxis behavior.
The olfactory system utilizes G protein-coupled receptors (GPCRs) to detect odorants. These receptors are called odorant receptors. Animals are able to use the olfactory system for chemotaxis. Chemotaxis involves direct navigation toward attractive chemicals and away from aversive chemicals. In order to be able to study the processing of olfactory data in the central nervous system (CNS), we chose a simple model organism that can be genetically manipulated; the fruit fly Drosophila melanogaster, and more specifically their larval state. We developed new spectroscopic methods to create stable odorant gradients in which odor concentrations were experimentally measured by Fourier transform infrared spectroscopy (FTIR). Using high-resolution behavioral analysis, we demonstrated that sensory input from both sides of the head increases the overall accuracy of navigation. This study was a collaboration between the Sakmar and Vosshall labs at the Rockefeller University.

Rapid incorporation of functional rhodopsin into nanoscale apolipoprotein bound bilayer (NABB) particles.
It is generally accepted that several G protein-coupled receptors (GPCRs) are dimeric proteins, which require dimerization for proper functionality. However, for the majority of GPCRs the situation is not that clear, and it is matter of intense debate, whether the functional unit of the visual photoreceptor rhodopsin is a monomer or a dimer. In this paper, we addressed this problem and developed novel nanoscale apolipoprotein bound bilayer (NABB) particles to study rhodopsin monomers and dimers with a controlled stoichiometry. The receptor in these NABB particles retains its exceptional stability against thermal denaturation, which renders these particles substantially better than detergent micelles used traditionally for isolated receptors. Moreover, we used single-particle electron microscopy techniques to visualize the relative orientation of the rhodopsin dimers in these NABBs. We concluded that neither the dimer is required nor particularly active compared to the monomer of rhodopsin, which consequently seems to be the functional unit.

G Protein-Coupled Receptors Self-Assemble in Dynamics Simulations of Model Bilayers.
The self-assembly process of membrane proteins in biomembranes has important implications for the structure and function of macromolecular complexes involved, for example, in signal transduction systems. It is possible to follow the self-assembly process by spectroscopic methods, such as fluorescence resonance energy transfer (FRET) experiments, which result in some sort of order parameter that allows quantitative comparison of related systems observed under similar conditions. These "wet" or "test tube" experiments do not provide detailed information on how the different molecules are interacting with each other to result in the observed phenomena. In order to overcome this fundamental problem, we started collaborating with Dr. Xavier Periole in the Marrink lab in Groningen, The Netherlands. They had developed a novel molecular dynamics simulation technique, called coarse-grained molecular dynamics (CGMD) that allows modeling of large assemblies of dozens of membrane proteins in membranes containing thousands of lipids. In this paper, we report the results of a larger set of simulations with different lipids, each several microseconds long. The results are in overall agreement with our experimental studies of these systems. The corresponding authors of this paper are Periole and Huber, who established this transatlantic collaboration, during which they met several times in either Groningen or New York, respectively.

Curvature and Hydrophobic Forces Drive Oligomerization and Modulate Activity of Rhodopsin in Membranes.
Biomembranes are complex structures with different membrane proteins embedded in a lipid matrix, frequently described by a fluid mosaic model. Many membrane proteins have the intrinsic propensity to self-assemble into dimeric pairs or higher-order structures. However, for a large number of membrane proteins, it is difficult to pinpoint their behavior in the sense that they would have a strict tendency to stay monomeric, that is, without assembling into higher-order structures, or to form dimers or larger oligomers. Visual rhodopsin is such a case. While some authors have reported that it forms rows of dimers in the native membranes with the dimers as the functional unit for signaling, others have rejected this position in favor of a strictly monomeric protein. In this study, our aim was to determine the role of the membrane bilayer in the process of self-assembly of rhodopsin. We used fluorescence resonance energy transfer (FRET) experiments to monitor rhodopsin self-assembly in membranes of controlled composition, and we were using UV-Vis spectroscopy to probe the ability of rhodopsin to form the active state in these membranes. Consistent with a hydrophobic mismatch mechanism, we found that lipid bilayers with a thickness different from the hydrophobic lenght of rhodopsin induce self-assembly of the receptors into dimers or higher-order oligomers. The unexpected result was that these receptor clusters appear to block activation of the receptors. This work was performed as a collaborative project between the Brown lab at the University of Arizona, Tucson, and the Sakmar lab at the Rockefeller University, New York. Botelho and Huber share the first authorship.

Membrane model for the GPCR rhodopsin: hydrophobic interface and dynamical structure.
The crystal structure of visual rhodopsin from the Palczewski group in the year 2000 was a hallmark event in structural biology. Rhodopsin is the light receptor in the rod cells of the retina in the back of the eyes. Rhodopsin is a transmembrane protein, which is embedded in membranes that are rich in lipids containing the omega-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA). The specific aim of this study was to characterize the interfaces of rhodopsin that are in contact with the membrane lipids and with water, respectively. It should be noted that the dynamical nature of biological membranes makes the structure of lipids and the protein-lipid interface inaccessible to standard techniques of structural biology, which rely on single, static conformations. Our approach of combining solid-state deuterium NMR experiments with computational molecular dynamics simulations, which we applied successfully to at least one other system (see reference 7), are the state-of-the-art method to investigate these receptors in a native-like biomembrane model. The paper describes a detailed analysis of the system, and we found some remarkable movements of some regions of the receptor once released from the "straight-jacket" of the densely packed crystalline environment. This paper is based on my research originally started in the Beyer lab at the University of Munich and mainly performed during my stay in the Brown lab at the University of Arizona, Tucson, AZ, first as postdoctoral fellow and later as a visiting scientist.

Structure of docosahexaenoic acid-containing phospholipid bilayers as studied by 2H NMR and molecular dynamics simulations.
Polyunsaturated fatty acids are essential nutrients for humans, which imply that they are similar to vitamines that need to be provided with the diet. There are two classes, omega-6 and omega-3, depending on the position of the first unsaturation or double bond in the acyl chain. Docosahexaenoic acid (DHA) is the most important omega-3 fatty acid, especially concentrated in fish oil. Deficiency has been linked to retinal and neural development, learning, neurological dysfunction including Alzheimer's disease, Parkinson's disease, Zellweger's syndrome, and schizophrenia, and diseases including atherosclerosis and cancer. Despite this large number of associated medical conditions, the molecule mechanism of action for DHA is largely unknown. One possible hypothesis is that lipids carrying DHA chains have unique physicochemical properties that modulate the material properties of the membranes they are most highly concentrated in, such as synaptosomal membranes in the brain or the retinal photoreceptor rod cells. In order to obtain insight into the chemical basis that governs these material properties, we developed a new force field to perform computer simulations of model membranes, comparing DHA with more regular monounsaturated fatty acyl chains. In addition to these computer simulations, we were studying the same systems using solid-state deuterium NMR experiments. It should be noted that the results of our study were published back-to-back with a competing study, and both were the first computational studies applying molecular dynamics (MD) simulations of DHA containing bilayer membranes. This paper covers several years of work performed in the Beyer lab at the University of Munich and the Brown lab at the University of Arizona, Tucson, AZ.

A solid-state NMR study of phospholipid-cholesterol interactions: sphingomyelin-cholesterol binary systems.
Cholesterol is an essential building block of animal cells, including those in the human body. However, excessively high levels of cholesterol are associated with coronary heart disease, atherosclerosis, cerebrovascular disease, and an increased risk for heart attack and stroke. Understanding the physiology and pathophysiology of cholesterol is one of the most important research topics today. In this study, our aims are to understand the interactions in the molecular complex of cholesterol and sphingomyelin, which is a characteristic complex that makes up so called "lipid rafts", and to determine the critical saturation limit for cholesterol before microscopic crystals form, which is thought to occur as a consequence of hypercholesterinemia . Lipid rafts are thought to be self-organizing microdomains in the plasma membrane of cells, which enable efficient organization of functional systems, for example, the macromolecular complexes used for signal transduction of hormonal signals. This study employs various solid-state NMR techniques including the novel method to prepare oriented membranes with defined water content (see paper 5). This study was a collaboration of the Klaus Beyer lab at the University of Munich and the James A Hamilton lab at Boston University.

A 2H NMR study of macroscopically aligned bilayer membranes containing interfacial hydroxyl residues.
Energy-conserving biological membranes (biomembranes) are fundamentally important in living organisms. The inner membrane of mitochondria is one of those membranes. Mitochondria (as outlined above for paper 1) are sometimes called the "cellular power plants". This function is intimately connected to the properties of the energy conserving biomembranes, that is, their ability to maintain concentration gradients for protons and other metabolites. In this study, we applied solid-state nuclear magnetic resonance (NMR) spectroscopy to investigate the properties of hydroxyl residues on phospholipids and cholesterol. Especially the hydroxyl residues of the acidic phospholipids phosphatidylglycerol and cardiolipin might be involved in lateral proton conducting "wires" that connect the different units of the energy conversion mechanism of the mitochondria; the Fo/F1-ATPase and the respiratory chain complexes, which together form a proton circuit that converts one form of chemical energy into another. For this study, we developed a novel method to prepare oriented membranes with defined water content. This method was subsequently used in several other studies. We found that these hydroxyl residues were unusually stable, and we attributed this stability to reduced water accessibility to those groups. In summary, these results are consistent with a special environment of these hydroxyl residues that could support their role as proton conducting wires along the surface of mitochondria, and other energy conserving biomembranes, such as those in chloroplasts and bacterial inner membranes.

Mixed micelle formation between gramicidin-S and a nonionic detergent: a nuclear magnetic resonance model study of peptide/detergent aggregation.
Gramicidin-S is an unusual peptide antibiotic that is currently not used in medicine. However, due to the increased resistance seen for classical antibiotics, as for example MRSA (Methicillin-resistant Staphylococcus aureus) and other multi drug resistant bacteria, research on other types of antibiotics (such as gramicidin-S) becomes more important. Here we tried to investigate the mechanism of how the antibiotic binds to nonionic detergent micelles, which can be seen as very simple models of the bacterial cell membranes. Nuclear magnetic resonance (NMR) spectroscopy experiments revealed changes in the acid and base catalysis of the hydrogen to deuterium exchange reaction of the peptide bonds, as well as changes in the proton and carbon-13 spin-lattice relaxation rates. Together these data indicate that upon binding the flexible ring structure of the cyclic peptide becomes more stable and the anchors to the oily core of the micelle with the valine, leucine, and d-phenylalanine side chains.

Contribution of copper binding to the inhibition of lipid oxidation by plasmalogen phospholipids.
Several vitamines, such as A, C, and E, are protecting the cells from the detrimental effects of oxidative damage. Especially susceptible to this damage are many lipids in biological membranes. Here we investigated the role of copper in some detailed mechanism of lipid damage, utilizing nuclear magnetic resonance (NMR) spectroscopy and biochemical assays. The study was performed in collaboration with the laboratory of Engelmann, and we have developed the NMR spectroscopy analytical methods employed.

Investigation of the microscopic structure of a biological membrane; numerical model calculations as a methodological extension of physical experiments.
A biological membrane is an enclosing layer that acts as a barrier within or around a cell. It is composed of a double layer of lipids and proteins. Such membranes typically define enclosed spaces or compartments in which cells may maintain a chemical or biochemical environment that differs from the outside. Biological membranes are of fundamental importance in all forms of life we know of. Despite this paramount importance, it is difficult to render a detailed picture of the structure of such a membrane, since it is liquid and highly dynamic. We have built a simulation system utilizing extensive supercomputer calculations providing an unprecedented microscopic view into a 'virtual reality' of biological membranes. In this way we were able to interpret and understand physical experiments.

Binding of nucleotides by the mitochondrial ADP/ATP carrier as studied by 1H nuclear magnetic resonance spectroscopy.
In cell biology, mitochondria are membrane-enclosed organelle found in most eukaryotic cells, i.e., in cells from fungi, plants, and animals including humans. Mitochondria are sometimes described as "cellular power plants" because they generate most of the cell's supply of adenosine triphosphate (ATP), used as a source of chemical energy. ATP may be viewed as a "charged battery", and ADP is its discharged counterpart. The recycling process that recharges ATP from ADP involves selective transport of ADP and ATP across the membranes of mitochondria. In this study we have shown how a so-called carrier protein provides a selectivity filter, excluding other similar compounds from interfering with the recharging process. The studies involved computational quantum mechanics calculations, and nuclear magnetic resonance (NMR) spectroscopy, a technique related to the medical diagnostic method of magnetic resonance imaging (MRI).

Previous high-performance computing projects.
Large-scale biomembrane simulations with NAMD2 at the Pittsburgh Supercomputing Center (PSC), Carnegie Mellon University, University of Pittsburgh, Pittsburgh, PA, at the National Center for Supercomputing Applications, Champaign, IL, and at other sites participating in the TeraGrid project of the National Science Foundation.
Migration of an IBM/SP-2 project to home-build LINUX clusters using MPICH and LAM with CHARMM and Charm with NAMD2. Development of parallel molecular dynamics code for AMBER: shared memory on SNI/KSR-1 for version 4.0, and TCGMSG message passing on SPARC workstation cluster for version 4.1. Performance optimization of MPI message passing routines in the PME code of AMBER 4.1 on an IBM/SP-2. Local adaptation of GAMESS-US to SP-2.

Awards:

National Science Foundation's Partnerships for Advanced Computational Infrastructure (NFS PACI) Medium Resource Allocation Committee (MRAC) Renewal grant MCB060033 Huber (PI) 2008-2009

"Ligand binding mechanism in the visual photoreceptor opsin, a G-protein-coupled receptor (GPCR)"
The long-term goal of our research is to provide comprehensive understanding of ligand recognition in seven-transmembrane (7-TM) helical G-protein coupled receptors (GPCRs). The determination of the first high resolution structure of a GPCR, the visual photoreceptor rhodopsin, in the year 2000 was a hallmark that enabled us to study GPCRs by molecular dynamics (MD) simulations. We built models of receptors in a native-like phospholipid bilayer environment. These all-atom models contain typically about 50,000 atoms, and can be routinely simulated on a sub-microsecond timescale using massive parallel processing (MPP) architectures on the TeraGrid, such as the PSC BigBen Cray XT3. Along with biochemical and biophysical experiments to map the thermodynamics of ligand binding in rhodopsin, this research aims at formulating methods to study the mechanism of ligand binding and recognition for GPCRs in general. In contrast to computational 'alchemy' studies to determine the absolute free energy of ligand binding, we utilize in a conceptual framework that focuses on thermally accessible ligand binding pathways and the role of receptor conformational changes in gating the ligand access. In the past year, publication of a series of high resolution crystal structures of additional GPCRs led to dramatic advances in the field. The new structures include β2-adrenergic receptor, squid rhodopsin, and most recently, opsin, the ligand-free form of bovine rhodopsin. Due to the importance of the β2-adrenergic receptor structure, we used the majority of the 300,000 service units (SUs) of from the previous application period to simulate several models of β2-adrenergic receptor with the inverse agonist carazolol and the natural agonist epinephrine (adrenaline) for more than 600 nanoseconds simulation time in total. Here we apply for TeraGrid Wide Roaming Access with 500,000 SUs in order to continue the studies on 11-cis-retinal binding to opsin, which we would like to supplement with comparative studies on ligand binding in β2-adrenergic receptor. The computational resources will be used for conventional MD simulations to study the equilibrium dynamics of several receptor structures, as well as for biased MD simulations to probe the free energy landscape of the ligand binding pathway.
Role: PI

Completed Research Support

National Science Foundation's Partnerships for Advanced Computational Infrastructure (NFS PACI) Medium Resource Allocation Committee (MRAC) Renewal grant MCB060033 Huber (PI) 2007-2008
"Ligand binding mechanism in the visual photoreceptor opsin, a G-protein-coupled receptor (GPCR)"
Role: PI

NFS PACI Medium Resource Allocation Committee (MRAC) grant MCB060033 Huber (PI) 2006-2007
"Ligand binding mechanism in the visual photoreceptor opsin, a G-protein-coupled receptor (GPCR)"
Role: PI

NSF PACI Development grant MCB020015P Huber (PI) 2002-2003
"Dynamics of phospholipids in G protein-coupled receptor containing membranes"
Role: PI

NSF PACI Development grant MCB020017N Huber (PI) 2002-2003
"Molecular dynamics simulations of a Biomembrane model comprising the G protein-coupled receptor rhodopsin in a polyunsaturated lipid bilayer membrane"
Role: PI

NSF PACI Alliance Allocations Board (AAB) grant MCB020034 Huber (PI) 2002-2003
"Rhodopsinthe single quantum detector and its unique environment"
Role: PI

NFS PACI Alliance Allocations Board (AAB) grant MCB030026 Huber (PI) 2003-2005
"Biomembrane models of G protein-coupled receptor signaling"
Role: PI

Published Papers

19).
Ye, S., Huber, T., R. Vogel, and Sakmar,T. P.
Azido labels enable FTIR analysis of rhodopsin activation.
Nat. Chem. Biol., 2009, 5:397-399.

PMID: 19396177 [PubMed - indexed for MEDLINE]

18).
Sakmar, T. P., and Huber, T.
Rhodopsin.
In New Encyclopedia of Neuroscience, Eds. L. R. Squire, Oxford: Academic Press, Elsevier, San Diego, CA. 2009, 8:365-372.

[not indexed for MEDLINE]

17).
Huber, T., Menon, S.T., and Sakmar, T.P.
Structural Basis for Ligand Binding and Specificity in Adrenergic Receptors: Implications for GPCR-targeted Drug Discovery.
Biochemistry, 2008, 47:11013-11023.

PMID: 18821775 [PubMed - indexed for MEDLINE]

16).
Huber, T., and Sakmar, T. P.
Rhodopsin's active state is frozen like a DEER in the headlights.
Proc. Natl. Acad. Sci. U.S.A., 2008, 105:7343-7344.

PMID: 18492801 [PubMed - indexed for MEDLINE]

15).
Ye, S. X., C. Köhrer, Huber, T., M. Kazmi, P. Sachdev, E. C. Y. Yan, A. Bhagat, U. L. RajBhandary, and Sakmar, T.P.
Site-specific incorporation of keto amino acids into functional G protein-coupled receptors using unnatural amino acid mutagenesis.
J. Biol. Chem., 2008, 283:1525-1533.

PMID: 17993461 [PubMed - indexed for MEDLINE]

14).
Vogel, R., M. Mahalingam, S. Lüdeke, Huber, T., F. Siebert, and Sakmar, T.P.
Functional role of the "ionic lock"—an interhelical hydrogen-bond network in family A heptahelical receptors.
J. Mol. Biol., 2008, 380:648-655.

PMID: 18554610 [PubMed - indexed for MEDLINE]

13).
Louis, M., Huber, T., R. Benton, T. P. Sakmar, and L. B. Vosshall.
Bilateral olfactory sensory input enhances chemotaxis behavior.
Nat. Neurosci., 2008, 11:187-199.

PMID: 18157126 [PubMed - indexed for MEDLINE]

12).
Banerjee, S., Huber, T., and Sakmar, T.P.
Rapid incorporation of functional rhodopsin into nanoscale apolipoprotein bound bilayer (NABB) particles.
J. Mol. Biol., 2008, 377:1067-1081.

PMID: 18313692 [PubMed - indexed for MEDLINE]

11).
Periole, X., Huber, T., S.-J. Marrink, Sakmar, T.P.
G Protein-Coupled Receptors Self-Assemble in Dynamics Simulations of Model Bilayers.
J. Am. Chem. Soc., 2007, 129:10126-10132.

PMID: 17658882 [PubMed - indexed for MEDLINE]

10).
Botelho, A. V., Huber, T., Sakmar, T. P., and M. F. Brown.
Curvature and Hydrophobic Forces Drive Oligomerization and Modulate Activity of Rhodopsin in Membranes.
Biophys. J., 2006, 91:4464-4477.

PMID: 17012328 [PubMed - indexed for MEDLINE]

9).
Huber, T., and Sakmar, T.P.
The Photoreceptor Membrane as a Model System in the Study of Biological Signal Transduction.
In Advances in Planar Lipid Bilayers and Liposomes, Eds. A. Ottava and H. T. Tien, Elsevier, San Diego, CA. 2005, 1:181-206.

[not indexed on PUBMED]

8).
Huber, T., A. V. Botelho, K. Beyer, and M. F. Brown.
Membrane model for the GPCR rhodopsin: hydrophobic interface and dynamical structure.
Biophys. J., 2004, 86:2078-2100.

PMID: 15041649 [PubMed - indexed for MEDLINE]

7).
Huber, T., K. Rajamoorthi, V. F. Kurze, K. Beyer, and M. F. Brown.
Structure of docosahexaenoic acid-containing phospholipid bilayers as studied by 2H NMR and molecular dynamics simulations.
J. Am. Chem. Soc., 2002, 124:298-309.

PMID: 11782182 [PubMed - indexed for MEDLINE]

6).
Guo, W., V. F. Kurze, Huber, T., N. H. Afdhal, K. Beyer, and J. A. Hamilton.
A solid-state NMR study of phospholipid-cholesterol interactions: sphingomyelin-cholesterol binary systems.
Biophys. J., 2002, 83:1465-1478.

PMID: 12202372 [PubMed - indexed for MEDLINE]

5).
Kurze, V. F., B. Steinbauer, Huber, T., and K. Beyer.
A 2H NMR study of macroscopically aligned bilayer membranes containing interfacial hydroxyl residues.
Biophys. J., 2000, 78:2441-2451.

PMID: 10777740 [PubMed - indexed for MEDLINE]

4).
Beyer, K., and Huber, T..
Mixed micelle formation between gramicidin-S and a nonionic detergent: a nuclear magnetic resonance model study of peptide/detergent aggregation.
Eur. Biophys. J. Biophys. Lett., 1999, 28:166-173.

[not indexed on PUBMED]

3).
Hahnel, D., Huber, T., V. F. Kurze, K. Beyer, and B. Engelmann.
Contribution of copper binding to the inhibition of lipid oxidation by plasmalogen phospholipids.
Biochem. J., 1999, 340:377-383.

PMID: 10333478 [PubMed - indexed for MEDLINE]

2).
Huber, T.
Untersuchungen zur mikroskopischen Struktur einer biologischen Membran numerische Modellrechnungen als methodische Erweiterung physikalischer Experimente.
Ph.D. thesis, 1999, Ludwig-Maximilians-Universität, München.

[not indexed on PUBMED]

1).
Huber, T., M. Klingenberg, and K. Beyer.
Binding of nucleotides by the mitochondrial ADP/ATP carrier as studied by 1H nuclear magnetic resonance spectroscopy.
Biochemistry, 1999, 38:762-769
PMID: 9888816 [PubMed - indexed for MEDLINE]

Recent Presentations

Invited Talks
Principles of molecular recognition in biomembranes. 2007. Department of Chemistry, City College of CUNY, New York, NY.

Thermodynamic analysis of the ligand binding pathway in the seven-transmembrane (7-TM) receptor rhodopsin. 2007. Biophysical Society Annual Meeting, Baltimore, MD.

Functional consequences of seven-transmembrane receptor association in bilayers. 2007. Biophysical Society Annual Meeting, Baltimore, MD.

Curvature and Hydrophobic Mismatch Drive Non-Ideal Mixing and Activation of Rhodopsin in Membranes. 2006. Biophysical Society Annual Meeting, Salt Lake City, UT.

Closing the visual cycle–exit and entry of retinal in opsin. 2006. Biophysical Society Annual Meeting, Salt Lake City, UT.

Visual Photoreceptor Membranes, New Challenges from a Classical System. 2004. Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Groningen, The Netherlands.

The hydrophobic interface of the GPCR prototype rhodopsin. 2002. Laboratory of Molecular Biology and Biochemistry, Rockefeller University, New York, NY.

Critical evaluation of influences of membrane lipid properties on rhodopsin function. 2002. Biophysical Society Annual Meeting, San Francisco, CA.

Mixed micelle formation between gramicidin-S and a nonionic detergent. 1997. Annual Meeting of the Sonderforschungsbereich 266, Schloß Ringberg Tagungsstätte der Max-Planck-Gesellschaft, Tegernsee, Germany.

Numerical simulations of a bilayer lipid membrane.
1996. Department of Chemistry, Penn State University, University Park, PA.
2000 Biophysical Society 44th Annual Meeting in New Orleans, LA
2001 Biophysical Society 45th Annual Meeting in Boston, MA
2002 Biophysical Society 46th Annual Meeting in San Francisco, CA
2003 Biophysical Society 47th Annual Meeting in San Antonio, TX
2004 Biophysical Society 48th Annual Meeting in Baltimore, MD
2005 Biophysical Society 49th Annual Meeting in Long Beach, CA
2006 Biophysical Society 50th Annual Meeting in Salt Lake City, UT
2007 Biophysical Society 51st Annual Meeting in Baltimore, MD
2008 Biophysical Society 52nd Annual Meeting in Long Beach, CA
2009 Biophysical Society 53rd Annual Meeting in Boston, MA

Posters

30).
Huber, T., S.-J. Marrink, and Sakmar, T.P. (2009).
Membrane proteins-bilayer interplay: insights from coarse-grained self-assembly and potential of mean force simulations of rhodopsin in model bilayers.
Biophys. J., 96, 673a.

29)
Ye, S., Huber, T., and Sakmar, T.P. (2009).
Unnatural amino acid mutagenesis for site-specific incorporation of keto and azido functionalities into functional G protein-coupled receptors.
Biophys. J., 96, 632a.

28)
Huber, T., Sakmar, T.P. (2009).
Structural basis of lipid effects on G-protein-coupled receptor (GPCR) activation.
Biophys. J., 96, 592a-593a.

27)
Banerjee, S., A. Grunbeck, Huber, T., P. Sachdev, and Sakmar, T.P. (2009).
Rapid incorporation of heterologously expressed GPCR CCR5 in nanoscale apolipoprotein bound bilayers (NABBs).
Biophys. J., 96, 51a.

26)
Ye, S., Huber, T., R. Vogel, Sakmar, T.P. (2009).
Probing conformational changes in rhodopsin with site-specific azido labels.
Biophys. J., 96, 6a.

25)
Huber, T, T. P. Sakmar, and L. Vosshall. (2009).
Mechanisms of chemotactic navigation in Drosophila larvae.
J. Neurogenetics, 23, S75-S75.

24)
Banerjee, S., Huber, T., and Sakmar, T.P. (2008).
Imaging Heptahelical Receptors in Nanoscale Apolipoprotein Bound Bilayers.
Biophys. J., 94, 477a.

23)
Huber, T., Sakmar, T.P.(2007).
Seven-transmembrane (7-TM) receptors self-assemble in coarse grain molecular dynamics (CGMD) simulations of model bilayers.
Biophys. J., 92, 250A.

22)
Huber, T., K. M. Gunnison, M. A. Kazmi, B. S. W. Chang, and Sakmar, T.P. (2007).
Thermodynamic analysis of the ligand binding pathway in the seven-transmembrane (7-TM) receptor rhodopsin.
Biophys. J., 92, 186A.

21)
Huber, T., A. V. Botelho, T. P. Sakmar, and M. F. Brown. (2007).
Functional consequences of seven-transmembrane receptor association in bilayers.
Biophys. J., 92, 198A.

20)
Huber, T., and Sakmar, T.P. (2006).
Chromophore Entry and Release in Visual Pigments.
Keystone Symposium on G Protein-Coupled Receptors: Evolving Concepts and New Techniques. (Talk).

19)
Huber, T., K. M. Gunnison, M. A. Kazmi, B. S. W. Chang, and Sakmar, T.P. (2006).
Closing the visual cycle – exit and entry of retinal in opsin.
Biophys. J. 90, 331a., 1599-Plat. (Talk).

18)
Huber, T., A. V. Botelho, T. P. Sakmar, M. F. Brown. (2006).
Curvature and Hydrophobic Mismatch Drive Non-Ideal Mixing and Activation of Rhodopsin in Membranes.
Biophys. J., 90, 15a. 64-Plat. (Talk).

17)
A. V. Botelho, V. F. Kurze, K. Beyer, M. F. Brown, and Huber, T.. (2006)
Collective Order Fluctuations from Deuterium NMR Studies of Hydration Effects on POPC–d31 Membranes.
Biophys. J., 90, 365a. 1744-Pos.

16)
Huber, T., K. M. Gunnison, M. A. Kazmi, B. S. W. Chang, and Sakmar, T.P. (2005).
Identification of the Primary Entry Site in Visual Rhodopsins: an Intramembranous Pathway from Mutagenesis and MD Simulations.
Biophys. J., 88, 2482-Pos.

15)
Botelho, A. V., Huber, T., T. P. Sakmar, and M. F. Brown. (2005).
Direct Effect of Membrane Stress on Lipid-Rhodopsin Organization and Function.
Biophys. J., 88, 2846-Pos.

14)
Banerjee, S., T. P. Sakmar, and Huber, T.. (2005.)
Incorporation of Rhodopsin into a Nanoscale Apolipoprotein Bound Bilayer.
Biophys. J., 88, 2845-Pos.

13)
Huber, T., B. S. W. Chang, A. V. Botelho, T. P. Sakmar, and M. F. Brown. (2004).
Phase space sampling – A long journey towards realistic biomembrane models.
Biophys. J., 86, 417a.

12)
Brown, M. F., A. V. Botelho, Huber, T., and H. I. Petrache. (2004).
Polyunsaturated bilayers: What's the difference?
Biophys. J., 86, 367a. (Talk).

11)
Botelho, A. V., Huber, T., and M. F. Brown. (2004).
Free energy additivity for modeling lipid-protein interactions.
Biophys. J., 86, 563a.

10)
Huber, T., B. S. W. Chang, and Sakmar, T.P. (2003).
Structure and Dynamics of Archosaur Rhodopsin and Other Ancestral Visual Pigments.
Biophys., J. 84, 271a.

9)
Huber, T., A. V. Botelho, and M. F. Brown. (2003).
Membrane Model for the GPCR Rhodopsin: Dynamical Structure and Generalized Molecular Surface.
Biophys. J., 84, 272a.

8)
Botelho, A. V., Huber, T., and M. F. Brown. (2003).
Flexible Surface Model for Lipid-Rhodopsin Interactions: Further Analysis.
Biophys. J., 84, 55a.

7)
Botelho, A. V., Huber, T., and M. F. Brown. (2002).
Lipid-Protein Interactions-New Biomembrane Model.
Biophys. J., 82,152a.

6)
Botelho, A. V., Huber, T., and M. F. Brown. (2002).
Hydrophobic Matching of Lipids and Rhodopsin in Membranes Probed by 2H NMR and Flash Photolysis Spectroscopy.
Biophys. J., 82,146a.

5)
Huber, T., A. V. Botelho, and M. F. Brown. (2002).
Hydrophobic interface of the GPCR prototype rhodopsin.
Biophys. J., 82, 225a.

4)
Huber, T., A. V. Botelho, and M. F. Brown. (2002).
Critical Evaluation of Influences of Membrane Lipid Properties on Rhodopsin Function.
Biophys. J., 82, 27a. (Talk)

3)
Huber, T., A. V. Botelho, K. Beyer, and M. F. Brown. (2002).
Structural Principles and Applications of 2H NMR and Molecular Dynamics to Biomembranes.
Biophys. J., 82, 152a.

2)
Beyer, K., V. F. Kurze, B. Steinbauer, and Huber, T.. (2000).
Interfacial membrane dynamics as studied by 2H-NMR using exchange labeled hydroxyl residues.
Biophys. J., 78, 181a.

1)
Huber, T., and K. Beyer. (2000).
Multiscale properties of the aqueous boundary of biological membranes from simulation.
Biophys. J., 78, 182a.

The Sakmar Laboratory

The Laboratory of
Molecular Biology & Biochemistry
at Rockefeller University

Neeraj Kapoor,
Graduate Student

Tri-Insitutional Program in Chemical Biology

Laboratory of Molecular Biology and Biochemistry
Rockefeller Research Building 510

The Rockefeller University, Box 187
1230 York Avenue
New York, NY 10065
Telephone: 212-327-8284
Fax: 212-327-7904

nkapoor@mail.rockefeller.edu

Curriculum Vitae

Education

Ph.D. in Biochemistry and Molecular Biology, Rockefeller University 2004-present
M.Sc. in Chemistry, Indian Institute of Technology, Kanpur 1999-2004

Research

Understanding the mechanism of Heterotrimeric G-protein activation
Heptahelical G protein-coupled receptors (GPCRs) couple to heterotrimeric G proteins to relay extracellular signals to intracellular signaling networks, but the molecular mechanism underlying GDP release by the G protein α-subunit is not well understood. The signal of activation is delivered to the G protein pocket via a5 helix, a microdomain on Ga protein which allosterically couples the conformational change necessary for nucleotide exchange to receptor activation. A number of theoretical as well as experimental models are available that explain various aspects of this process but still the overall understanding of the activation process is incomplete. We have utilized both structural biology and Spectroscopic methods to address this question by studying single amino acid point mutants of a5 helix residues with multifold increased rates of basal nucleotide exchange. Using X-ray crystallography we have been able to trap an intermediate along the activation pathway which has led us to propose a “sequential-release” mechanism for the activation of Heterotrimeric G proteins.

Mechanistic understanding of the modulatory effect of Calnuc, a novel Ca2+ binding protein towards G protein activation
Calnuc is a novel golgi-resident Ca2+ binding protein that has been shown to interact with the a5 helix of Ga proteins. Since it is well established that a5 helix delivers the receptor mediated activation signal to the catalytic pocket to facilitate nucleotide exchange, we are very much interested in understanding the functional relevance of this interaction. We have established heterologous expression system for both Calnuc and Gai1. Our analysis shows the interaction is dependent both on the Ca2+ bound state of Calnuc and the specific nucleotide bound state of G protein. The exact in vitro functional relevance of this selective interaction is under investigation. We also wish to understand the exact molecular determinants of this interaction and the physiological relevance of the regulation.

Investigation of the Anti-amyloidogenic properties of Calnuc
Calnuc, a novel Ca2+ binding protein has been shown to be substantially upregulated in brains of patients suffering from Alzheimer’s disease (AD). It has also been shown that Calnuc can interact with the Amyloid Precursor Protein (APP), the transmembrane protein whose proteolytic product Ab42 is implicated in the pathology of AD. We are interested in investigating the functional efficacy of Calnuc towards inhibting the aggregation of Ab42 into fibrils and towards dissociation of preformed fibrils both in an in vitro and in vivo setup. We also wish to extend the work to other amyloidogenic peptides like hIAPP, implicated in Type-2 diabetes mellitus.

Published Papers
1).
Kapoor, N., Menon, S.T., Chauhan, R., Sachdev, P. & Sakmar, T.P.
Structural Evidence for a Sequential Release Mechanism for Heterotrimeric G protein activation
Journal of Molecular Biology,2009, In Press

[not indexed on PUBMED]

Posters:
1).
Heterotrimeric G-Proteins
Rockefeller University Chemical Biology retreat, May 19-21, 2009

The Sakmar Laboratory

The Laboratory of
Molecular Biology & Biochemistry
at Rockefeller University

Manija Kazmi

Research Specialist & Laboratory Manager

Laboratory of Molecular Biology and Biochemistry

Rockefeller Research Building 510
The Rockefeller University, Box 187
1230 York Avenue
New York, NY 10065

Telephone: 212-327-8284
Fax: 212-327-7904

kazmim@mail.rockefeller.edu

Biosketch

Education

M.S. in Molecular Biology, New York University 1997
B.S. in Biology, Queens College 1992

Research

My role in the lab is now primarily lab manager. I mainly assist other lab members with their ongoing projects. My most recent research has been to elucidate the function of pepducins, which are novel cell-penetrating peptides that act as inhibitors of signalling from receptors to G proteins.

Published Papers

15).
Ye S., Köhrer C., Huber T., Kazmi M., Sachdev P., Yan E.C., Bhagat A., RajBhandary U.L., Sakmar T.P.
Site-specific incorporation of keto amino acids into functional G protein-coupled receptors using unnatural amino acid mutagenesis.
J Biol Chem 283: 1525-33 (2008)

PMID: 17993461 [PubMed - indexed for MEDLINE]

14).
Lewis, J.W., Szundi, I., Kazmi, M.A., Sakmar, T.P., & Kliger, D. S.
Proton movement and photointermediate kinetics in rhodopsin mutants
Biochemistry 45: 5430-9 (2006)

PMID: 16634624 [PubMed - indexed for MEDLINE]

13).
Su, C.Y., Luo, D.G., Terakita, A., Shichida, Y., Liao, H.W., Kazmi, M.A., Sakmar, T.P., & Yau, K.W.
Parietal-eye phottransduction components and their potential evolutionary implications
Science 311: 1617-21 (2006)

PMID: 16543463 [PubMed - indexed for MEDLINE]

12).
Lewis, J.W., Szundi, I., Kazmi, M.A., Sakmar, T.P., and Kliger, D.S.
Time-resolved photointermediate changes in rhodopsin glutamic acid 181 mutants
Biochemistry 43: 12614-21 (2004)

PMID: 15449951 [PubMed - indexed for MEDLINE]

11).
Yan, E. C., Ganim, Z., Kazmi, M. A., Chang, B. S. W., Sakmar, T. P. & Mathies, RA
Resonance Raman Analysis of the Mechanism of Energy Storage and Chromophore Distortion in the Primary Visual Photoproduct
Biochemistry 43:10867-10876 (2004)

PMID: 15323547 [PubMed - indexed for MEDLINE]

10).
Yan, E. C., Kazmi, M. A., Ganim, Z., Hou, J. M., Pan, D., Chang, B. S. W., Sakmar, T. P. & Mathies, R. A.
Retinal Counterion Switch in the Photoactivation of the G Protein-Coupled Receptor Rhodopsin
Proc Natl Acad Sci U S A 100:9262-9267 (2003)

PMID: 12835420 [PubMed - indexed for MEDLINE]

9).
Chang, B.S.W., Jonsson K., Kazmi, M.A., Donoghue, M.J., and Sakmar, T.P.
Recreating a functional ancestral archosaur visual pigment
Mol. Biol. Evol. 19: 1483-9 (2002)

PMID: 12200476 [PubMed - indexed for MEDLINE]

8).
Yan, E. C., Kazmi, M.A., De S., Chang, B. S. W., Seibert, C., Marin E. P., Mathies, R.A., and Sakmar, T.P.
Function of extracellular loop 2 in rhodopsin: glutamic acid 181 modulates stability and absorption wavelength of metarhodopsin II
Biochemistry 19:3620-7 (2002)

PMID: 11888278 [PubMed - indexed for MEDLINE]

7).
Chang, B.S.W., Manija A. Kazmi and Thomas P. Sakmar.
Synthetic gene technology: Applications to ancestral gene reconstruction and structure-function studies of receptors
Methods in Enzymology 343: 274-94 (2002)

PMID: 11665573 [PubMed - indexed for MEDLINE]

6).
Kazmi, M.A., L.A. Snyder, A.M. Cypess, S.G. Graber, T.P. Sakmar.
Selective reconstitution of human D4 dopamine receptor variants with Gi alpha subtypes
Biochemistry 39:3734-44 (2000)

PMID: 10736173 [PubMed - indexed for MEDLINE]

5).
Ostrer, H., R.K. Pullarkat, and M.A. Kazmi.
Glycosylation and palmitoylation are not required for the formation of the X-linked cone opsin visual pigments
Mol. Vis. 10;4:28 (1998)

PMID: 9852167 [PubMed - indexed for MEDLINE]

4).
Ostrer, H., and M.A. Kazmi.
Mutation of a conserved proline disrupts the retinal-binding pocket of the X-linked cone opsins
Mol. Vis. 29; 3:16 (1997)

PMID: 9479007 [PubMed - indexed for MEDLINE]

3).
Kazmi, M.A., T.P. Sakmar, and H. Ostrer.
Mutation of a conserved cysteine in the X-linked cone opsins causes color vision deficiencies by disrupting protein folding and stability
Invest. Ophthalmol. Vis. Sci. 38:1074-81 (1997)

PMID: 9152227 [PubMed - indexed for MEDLINE]

2).
Kazmi, M. A., Dubin, R. A., Oddoux, C., and Ostrer, H.
High-level expression of visual pigments in transfected cells
Biotechniques 21:304-311 (1996)

PMID: 8862817 [PubMed - indexed for MEDLINE]

1).
Dubin R. A., Kazmi M. A., Ostrer H.
Inverted repeats are required for circularization of the mouse Sry transcript
Gene 167:245-248 (1995)

PMID: 8566785 [PubMed - indexed for MEDLINE]

Posters

8).
Ye, S.; Huber, T., Sakmar, T.P.
Fluorescent Labeling of GPCRs by the Site Specific Incorporation of Keto and Azido Amino Acids.
Biophysical Society Meeting, Boston, US, March, 2009.

7).
Ye, S.; Huber, T., Sakmar, T.P.
Site-Specific Labeling of Heptahelical Receptors Containing Keto and Azido Amino Acids.
Keystone symposia, Cambridge, UK, September, 2008.

6).
Ye, S.; Huber, T., Sakmar, T.P.
Fluorescent Labeling of GPCRs by the Site Specific Incorporation of Unnatural Amino Acids.
Rockefeller University Postdoctoral Retreat, New York, September 2007 and 2008.

5).
Ye, S.; Strzalka, J.W., Discher, B.M.; Noy, D., Moser, C.C.; Dutton, P.L., Blasie, J.K.
Design and characterization of artificial integral membrane proteins for vectorial electron transfer across soft interfaces.
226th ACS National Meeting, New York, September, 2004.

4).
Ye, S.; Strzalka, J.W., Churbanova, I.Y., Johansson, J.S., Blasie, J.K.
Model Membrane Protein for Binding Volatile Anesthetics.
48th Biophysical Society Annual Meeting, Baltimore, February, 2004.

3).
Ye, S.; Discher, B.M., Strzalka, J.W., Moser, C.C., Dutton, P.L., Blasie, J.K.
Design and physical characterization of vectorially oriented minimal electron-transfer protein monolayer at the air/water interface.
ACS National Meeting, New York, September, 2003.

2).
Ye, S.; Discher, B.M., Strzalka, J.W., Moser, C.C., Dutton, P.L., Ocko, B.M., Blasie, J.K.
Design and Physical Characterization of Vectorially Oriented Heme-Binding Peptide Monolayer.
36th Middle Atlantic Regional Meeting of ACS, Princeton, June, 2003.

1).
Ye, S.; Discher, B.M., Chen, X.X., Moser, C.C., Dutton, P.L., Ocko, B.M., Blasie, J.K.
Maquette Peptide Design and Its Applications in Biomaterial Engineering.
Institute of Medicine and Engineering of the University of Pennsylvania Annual Meeting, Philadelphia, Pennsylvania, December, 2001.

The Sakmar Laboratory

The Laboratory of
Molecular Biology & Biochemistry
at Rockefeller University

Adam Knepp
Biomedical Fellow
RU Graduate Program

Laboratory of Molecular Biology and Biochemistry

Rockefeller Research Building 510
The Rockefeller University, Box 187
1230 York Avenue
New York, NY 10065

Telephone: 212-327-8284
Fax: 212-327-7904
aknepp@rockefeller.edu

Curriculum Vitae

Education

Graduate Fellow, Rockefeller University, September 2008 – present
B.S. in Chemistry, Stanford University, 2008

Research

Single Molecule Analysis of Chemokine Receptor Complexes
Nature has evolved a remarkably complex signaling network of chemokines and chemokine receptors in order to coordinate the recruitment and activation of immune cells necessary for response. In addition to their normal physiological functions, these complexes are of great interest for their roles in a number of pathologies, including autoimmune disorders, pulmonary diseases, cancer, vascular diseases, and HIV. I am interested in developing chemical and biophysical tools to study the structural dynamics of these important proteins at a single molecule level. Information on how these complexes assemble and disassemble would greatly assist ongoing therapeutic efforts.

Awards

Honorable Mention, National Science Foundation Graduate Research Fellowship, 2009
Graduated from Stanford University with Distinction, 2008
VPUE Summer Research Grant, Stanford University, 2007
Physical Sciences Institute, Sandia National Laboratories, 2005-2006

Published Papers

2).
Ismail, H; Abel, PR; Green, WH; Fahr, A; Jusinski, LE; Knepp, AM; Zador, J; Meloni, G; Selby, TM; Osborn, DL; Taatjes, CA
Temperature-dependent kinetics of the vinyl radical (C2H3) self-reaction
J. Phys. Chem. A, 113, 1278-1286 (2009).

PMID: 19146471 [PubMed]

1).
Knepp, AM; Meloni, G; Jusinski, LE; Taatjes, CA; Cavalotti, C; Klippenstein, SJ
Theory, measurements, and modeling of OH and HO2 Formation in the reaction of cyclohexyl radicals with O2
Phys. Chem. Chem. Phys., 9, 4315-4331 (2007).

PMID: 17687479 [PubMed - indexed for MEDLINE]

Posters

3).
Hall, E.; Kim, S.; Knepp, A.M.
"A Microfluidic Platform for the Culture & Analysis of Single Cells."
2008 Biophysical Society Meeting.

2).
Knepp, A. M.; Meloni, G.; Jusinski, L. E.; Taatjes, C. A.
“Measurements of Product Formation in the Reaction of Cyclohexyl Radicals with O2.”
2007 Western Spectroscopy Association Conference.

1).
Jusinski, L. E.; Knepp, A. M.; Taatjes, C. A.
“Measurements of the Rate Constant of the Vinyl Radical Self-Reaction Between 298 and 600 K.”
2005 International Conference of Chemical Kinetics.

The Sakmar Laboratory

The Laboratory of
Molecular Biology & Biochemistry
at Rockefeller University

Faculty:

Christoph Seibert
•Ph.D., Humboldt University, Berlin
•Assistant Professor (2004 – 2008)
•Post-doctoral Associate (1999 – 2004)

Elsa Yan
•Ph.D., Columbia University
•Assistant Professor (2004 – 2007)
•Post-doctoral Associate (2000 – 2004)

Belinda S. W. Chang
•Ph.D., Harvard University
•Assistant Professor (2002 – 2003)
•Post-doctoral Associate (1999 – 2002)

Post-Doctoral Trainees:

Shixin Ye
•Ph.D. in Chemistry, University of Pennsylvania
•B.S. in Chemistry, Peking University
•Ph.D., Postdoctoral Associate (2004-2009)

T. R. Santosh Menon
•Ph.D., Indian Institute of Technology, Bangalore
•Post-doctoral Associate (1999 – 2009)

Fabien Décaillot
•Ph.D., Louis Pasteur University, Strasbourg, France
•Post-doctoral Associate (2008 – 2009)

Jay Janz
•Ph.D., Oregon Health and Science University
•Post-doctoral Associate (2004 – 2007)

Michael Rosconi
•Ph.D., SUNY–Stony Brook
•Post-doctoral Associate (2005 – 2006)

Andre Hoelz
•Ph.D., Rockefeller University
•Post-doctoral Associate (2003 – 2004)

A. Gopal Krishna
•Ph.D., Indian Institute of Technology, Poona
•Post-doctoral Associate (1998 – 2003)

Soma De
•Ph.D., Indian Institute of Technology, Bangalore
•Post-doctoral Associate (2000 – 2003)

Christopher Heise
•Ph.D., University of Virginia
•Post-doctoral Associate (2002 – 2003)

Jian-nong Feng
•Ph.D., Rockefeller University
•Post-doctoral Associate (2002 – 2003)

Harvey Jian-Min Hou
•Ph.D., Peking University, Peking, China
•Post-doctoral Associate (2001 – 2002)

Youwei Jiang
•Ph.D., City University of New York
•Post-doctoral Associate (1999 – 2002)

Stephen W. Lin
•Ph.D., University of California at Berkeley
•Post-doctoral Associate (1994 – 1999)

Lenore A. Snyder
•Ph.D., City University of New York
•Post-doctoral Associate (1994 – 1998)

Qing Zeng
•Ph.D., Louisiana State University
•Post-doctoral Associate (1996 – 1998)

Stephen A. Gravina
•Ph.D., Case Western Reserve University
•Post-doctoral Associate (1994 – 1997)

May Han
•Ph.D., Yale University
•Post-doctoral Associate (1996 – 1997)

Tatyana Zyvaga
•Ph.D., Shemyakin Institute, Russia
•Post-doctoral Associate (1992 – 1996)

Sophia Arnis
•Ph.D., Ludwigs-Universität, Freiburg, Germany
•Post-doctoral Associate (1994 – 1995)

Karim Fahmy
•Pd.D., Ludwigs-Universität, Freiburg, Germany
•Post-doctoral Associate (1991 – 1994)

Padmaja Deval
•Ph.D., Indian Institute of Technology, Bombay
•Post-doctoral Associate (1991 – 1993)

Oliver P. Ernst
•Diploma in Chemistry, Albert-Ludwigs-Universität, Freiburg, Germany
•Ph.D., Biochemistry/Biophysics, Albert-Ludwigs-Universität, Freiburg, •Germany
•Visiting Graduate Student (1993 - 1994)

Graduate Student Trainees:

Sourabh Banerjee
•B.S., Indian Institute of Technology, Delhi, India
•Graduate Fellow in Chemical Biology (2004 – 2008)

Nikhil Singla
•B.A., Cambridge University, Cambridge, UK
•Graduate Fellow in Chemical Biology

Adrian Lee
•B.S., University of Toronto, Toronto, Canada
•Graduate Fellow in Chemical Biology (2003 – 2004)

Ethan P. Marin
•B.A., Williams College; M.A., Unversity of Michigan
•M.D. - Ph.D. Biomedical Fellow (1996 – 2001)

Aaron M. Cypess
•A.B., Princeton
•M.D. - Ph.D. Biomedical Fellow (1994 – 1999)

K. Chrisopher Min
•A.B., Harvard College
•M.D. - Ph.D. Biomedical Fellow (1991 – 1996)

Rotation Graduate Students & Undergraduate Student Trainees:

Theresa Chan
•B.A., Smith College; M.D., Cornell Medical College, New York, NY;
•Pathology Resident, Johns Hopkins, Baltimore, MD;
•Summer Student (1991, 1992)

Mareike Beck
•Diplome, Freiburg University, Freiburg, Germany;
•Ph.D., Institut für Biophysik und Strahlenbiologie, Albert-Ludwigs-Universität, Freiburg, Germany;
•Summer Student (1992)
•Assistant for Research (1993 - 1994)

Matthew Albert
•Rotation Student 1993
B.A., Brown University, Providence, RI; Ph.D., Rockefeller University, New York, NY; M.D., Weill Medical College, New York, NY; Present Position, Pathology Resident, New York Presbyterian Hospital, New York, NY.

Nina Kim
•Harvard College

Mariya Minkova
•M.I.T.

Yu Wong
•University of Chicago

Kate Carroll
•University of California-Berkeley

Richard Lee
•Duke University

Dorothy Wang
•Harvard College

Thomas Nguyen
•Harvard College

Juergen Isele
•Ludwigs-Universität, Freiburg, Germany

Evan Muse
•Univ. of North Carolina

Angie You
•Harvard College

Oliver Ernst
•Ludwigs-Universität, Freiburg, Germany

Eugene Simuni
•Harvard College

V. Archambault
•McGill University, Montreal, Canada

Karolina Jönsson
•Univ. of Kalmar, Kalmar, Sweden

Tracy Terry
•Stanford University

Heather Baker
•Cornell University

Qian Yin
•Cornell University

Nicole Lehmann
•Freiburg University

Steffen Luedeke
•Freiburg University

Tobias Stuwe
•Heidelberg University, Heidelberg, Germany

Kathryn Morris
•University of Michigan

David Kastner
•Yeshiva University

Melissa Rampino
•New York University

Brian Zoltowski
•Cornell University

Amrita Hazra
•Cornell University

Marshall Miller
•Oregon State University

Jackie Wurst
•Cornell University

Guilio Quarta
•New York University

M. Chandramouli
•New York University

Disan Davis
•Carlton College

Dennis Kappei
•École Normale Supérieure, Paris, France

Aditi Bhagat
•Hunter College

M. Mahalingam
•Ludwigs-Universität, Freiburg, Germany

He Tian
•Peking University, Peking, China

The Sakmar Laboratory

The Laboratory of
Molecular Biology & Biochemistry
at Rockefeller University

Amy Ying Lin

Intern

Laboratory of Molecular Biology and Biochemistry

Rockefeller Research Building 510

The Rockefeller University, Box 187
1230 York Avenue
New York, NY 10065

Telephone: 212-327-8284
Fax: 212-327-7904

email@rockefeller.edu

Curriculum Vitae

Education

Research

Awards

Published Papers

Presentations

Posters

The Sakmar Laboratory

The Laboratory of
Molecular Biology & Biochemistry
at Rockefeller University

Marguerite Mangin

Senior Research Associate;
Academic Programs Director for the President's Office

Laboratory of Molecular Biology and Biochemistry
Rockefeller Research Building 510

The Rockefeller University, Box 187
1230 York Avenue
New York, NY 10065

Telephone: 212-327-8284
Fax: 212-327-7904
email@rockefeller.edu

Curriculum Vitae

Education

Marguerite received her B.S.-M.S. degree in Biochemistry from the University of Paris VI, and her Ph.D. degree in Molecular Biology from the University of Paris VII, completing her thesis in the Laboratory of Molecular Genetics of Georgio Bernardi at the Institut Jacques Monod, France. She conducted postdoctoral research in the laboratory of Alan M. Weiner, in the Department of Molecular Biophysics and Biochemistry at Yale University and was Research Scientist in the laboratory of Arthur E. Broadus, in the Department of Endocrinology at the Yale University School of Medicine. She has previously served as both Assistant and Associate Dean of Graduate Studies at The Rockefeller University and is currently its Director of Special Projects.

Research

Awards

Published Papers

Presentations

Posters

The Sakmar Laboratory

The Laboratory of
Molecular Biology & Biochemistry
at Rockefeller University

Parag Mukhopadhyay

Postdoctoral Fellow

Laboratory of Molecular Biology and Biochemistry

Detlev W. Bronk Building, 502
The Rockefeller University, Box 187
1230 York Avenue
New York, NY 10065

Telephone: 212-327-8283
Fax: 212-327-7904

pmukhopadh@rockefeller.edu

Curriculum Vitae

Education

Postdoctoral Associate, Rockefeller Universitry, March, 2009 - present
Ph.D. in Chemistry Duke University,USA, 2008
M.S. in Biological Sciences University of Calgary, Canda, 2003
M.S. in Chemistry Indian Institute of Technology, Delhi, India, 2001
B.S. in Chemistry University of Delhi, India, 1999

Research

Probing the molecular plasticity of chemokine:receptor macromolecular complex.
Chemokines are protein molecules that are critical mediators of cell migration during routine immune surveillance, inflammation, and development. Despite the pivotal role of chemokines in the immune system, these proteins are also associated with a large number of pathologies. For example, chemokine and their receptors (binding partners) participate in a number of human disease states including HIV/AIDS and cancer. Thus, chemokines are subjects of significant medical importance. We aim to understand the structural basis of the biological function of chemokines, which will help to develop chemical and biochemical methodologies for in vivo modulation of chemokine for therapeutic applications.
Research@Duke University:

Stereochemical analysis of chiral molecules in solution using chiroptical spectroscopy.
Modern chemistry emerged from the quest to describe the three-dimensional (3D) structure of molecules: van’t Hoff’s tetravalent carbon placed symmetry and dissymmetry at the heart of chemistry. We used modern chiroptical theory to elucidate the symmetry and dissymmetry of molecules and their assemblies. Chiroptical spectroscopy, including optical rotatory dispersion, electronic circular dichroism, vibrational circular dichroism, and Raman optical activity, measures the response of dissymmetric structures to electromagnetic radiation. This response can in turn reveal the arrangement of atoms in space, but deciphering the molecular information encoded in chiroptical spectra requires an effective theoretical approach. The computation of chiroptical signatures, in close coordination with synthesis and spectroscopy, provides a powerful framework to diagnose and to interpret the dissymmetry of chemical structures and molecular assemblies. We used chiroptical theory to elucidate 3D structures of molecules in solution, and explain how dissymmetry is templated and propagated in the condensed phase (Figure 2).

Awards

Departmental recognition award, Department of Chemistry, Duke University, 2007, for my research article published in Angewandte Chemie International Edition, where it also received the “Very Important Paper” designation; the work was also highlighted in Science (2007, 317:725) and Chemical and Engineering News (6 August, 2007).

Kathleen Zielek Fellowship for “Excellence in Research”, Department of Chemistry, Duke University, 2007.

Conference travel award, Graduate School, Duke University, 2007 and 2008.

Charles Bradsher Endowment Award for “Outstanding Graduate Student in Chemistry”, Department of Chemistry, Duke University, 2006.

Graduate School Research Scholarship, University of Calgary, 2003.

Competitive based admission to a summer school in theoretical and computational biophysics, Beckman Institute, University of Illinois at Urbana Champaign, 2003.

Graduate School differential fee award, University of Calgary, 2001.

Published Papers

7).
P. Mukhopadhyay, P. Wipf, D.N. Beratan
Optical signatures of molecular dissymmetry: Combining theory with experiments to address stereochemical puzzles.
Accounts of Chemical Research, 2009, ASAP.[Full text available]

PMID: 19378940 [PubMed - in process]

6).
P. Mukhopadhyay, G. Zuber, D.N. Beratan
Characterizing aqueous solution conformations of a peptide backbone using Raman optical activity computation.
Biophysical Journal, 2008, 95:5574-5586.

PMID: 18805935 [PubMed - indexed for MEDLINE]

5).
P. Mukhopadhyay, G. Zuber, P. Wipf, D.N. Beratan
Contribution of a solute’s chiral solvent imprint to optical rotation.
Angewandte Chemie International Edition, 2007, 46:6450-6452.

PMID: 17645276 [PubMed]

4).
P. Mukhopadhyay, G. Zuber, M. R. Goldsmith, P. Wipf, D.N. Beratan
Solvent effects on optical rotation: A case study of methyloxirane in water.
ChemPhysChem. 2006, 7:2483-2486.

PMID: 17072929 [PubMed - indexed for MEDLINE]

3).
P. Mukhopadhyay, L. Monticelli, D.P. Tieleman.
Molecular dynamics simulation of a palmitoyloleoyl-phosphatidylserine bilayer with Na+ counterions and NaCl
Journal Citation: Biophysical Journal, 2004, 86:1601-1609.

PMID: 14990486 [PubMed - indexed for MEDLINE]

2).
P. Mukhopadhyay, H. J. Vogel, D.P. Tieleman.
Distribution of pentachlorophenol in phospholipid bilayers: A molecular dynamics study
Biophysical Journal, 2004, 86:337-345.

PMID: 14695275 [PubMed - indexed for MEDLINE]

1).
J.L. MacCallum, P. Mukhopadhyay, H. Luo, D.P. Tieleman
Large scale molecular dynamics simulations of lipid-drug interactions.
Proceedings of the 17th Annual International Symposium on High Performance Computing Systems and Applications and the OSCAR Symposium, David Senechal (editor), NRC Research Press, Ottawa, Canada, 2003.

[not indexed on PUBMED]

Presentations

Southeastern Regional Meeting of the American Chemical Society, November 2008.

Laboratory of Molecular Biology and Biochemistry, The Rockefeller University, October 2008.

Roche, Palo Alto, July 2008.

Structural Biology and Biophysics Program, Duke University, May 2007 and April 2008.

Graduate School Research Day, Duke University, April 2008.

Department of Biological Sciences, University of Calgary, January and December2002.

Department of Chemistry, Indian Institute of Technology, Delhi, January 2000.

Posters

4).
P. Mukhopadhyay, Zuber, G., Wipf, P., and Beratan, D. N.,
“Modeling chiroptical properties of molecules in solution”,
233rd National American Chemical Society Meeting, Chicago, March 2007.

3).
P. Mukhopadhyay, Zuber, G., Goldsmith M. R., and Beratan, D. N.,
“Modeling solvent effects on optical rotation of chiral molecules”,
Symposium on Photonics at the Frontiers of Science and Technology, Fitzpatrick Center, Duke University, September 2006.

2).
P. Mukhopadhyay, Vogel, H. J., and Tieleman, D. P.,
“Distribution of pentachlorophenol between water and phospholipids bilayes: A molecular dynamics study”,
Biophysical Society Annual Meeting, San Antonio, February 2003.

1).
P. Mukhopadhyay and Tieleman, D. P.,
“Molecular dynamics simulation of negatively charged phospholipids bilayer”,
Canadian Society for Biochemistry, Molecular, and Cellular Biology Annual Meeting and International Symposium on Membrane Proteins in Health and Disease, Banff, March 2002.

The Sakmar Laboratory

The Laboratory of
Molecular Biology & Biochemistry
at Rockefeller University

Saranga Naganathan

Postdoctoral Fellow

Laboratory of Molecular Biology and Biochemistry

Detlev W. Bronk Building, 502
The Rockefeller University, Box 187
1230 York Avenue
New York, NY 10065

Telephone: 212-327-8283
Fax: 212-327-7904

snaganatha@rockefeller.edu

Curriculum Vitae

Education

Postdoctoral Researcher, The Rockefeller University, 2009 - present
Ph.D. in Biochemistry, University of Maryland, College Park, 2003-2008
M.Sc. in Advanced Biochemistry, University of Madras, India , 2002-2003
B.S. in Physics, University of Madras, India, 1999-2002

Research

Chemokine receptors belong to the heptahelical transmembrane G-protein coupled receptor family of membrane proteins. I am currently involved in two research projects focused on the chemokine receptors CXCR4, CXCR7 and CCR5.

(1) Investigating the roles of CXCR4 and CXCR7 in tumor growth and metastasis, in particular understanding their selective signaling pathways.

(2) To probe the GPCR, CCR5 by site specific incorporation of unnatural amino acids using the amber codon suppression technology combined with fluorescent labeling. We are now developing a labeling technique suitable for fluorescent imaging and detection of GPCRs in live cells. This methodology is also aimed at directly probing GPCRs to investigate conformational changes associated with agonist interaction.

Awards

Dr. Herman Kraybill Biochemistry Fellowship,University of Maryland, College Park (2006)

Bioscience Day Poster Competition Winner, University of Maryland. (2005)

UMD College Travel Award, University of Maryland. (2004)

University Rank Holder, Bachelor of Science, University of Madras. (2002)

Published Papers:

2.)
Zhao H, Naganathan S, Beckett D
Thermodynamic and structural investigation of bispecificity in protein-protein interactions.
J Mol Biol. 2009 Jun 5; 389(2):336-48

PMID: 19361526 [PubMed - indexed for MEDLINE]

1).
Naganathan, S., and Beckett, D.
Nucleation of an allosteric response via ligand-induced loop folding.
J Mol Biol. 2007 Oct 12; 373 (1): 96-111

PMID: 17765263 [PubMed - indexed for MEDLINE]

The Sakmar Laboratory

The Laboratory of
Molecular Biology & Biochemistry
at Rockefeller University

Pallavi Sachdev

Research Associate

Laboratory of Molecular Biology and Biochemistry

Rockefeller Research Building 510
The Rockefeller University, Box 187
1230 York Avenue
New York, NY 10065

Telephone: 212-327-8284
Fax: 212-327-7904

sachdep@rockefeller.edu

Curriculum Vitae

Education

2002-2007 - Postdoctoral Associate, The Rockefeller University
1996-2002 - Ph.D. in Biochemistry and Molecular Biology, Mount Sinai-New York University School of Medicine,
1996 - M.P.H. in Epidemiology and Biostatistics, New York Medical College, Graduate School of Health Sciences,
1993 - B.S. in Biological Sciences, Cornell University

Research

Role of chemokine receptors CXCR4 and CXCR7 in tumor growth and metastasis
Allosteric modulation of G protein coupled receptors by receptor dimerization
Role of non-canonical heterotrimeric G protein signaling pathways in cell growth and differentiation

Awards

Tri-Institutional Stem Cell Initiative, 2006
Murray Foundation Research Grant, 2005
National Institutes of Health, National Eye Institute Vision Training Grant, 2002-2003

Published Papers:

10)
Sachdev, P., Tirunagari, L.M., Kappei, D., Unson, C.G. (2009)
Monitoring glucagon and glucagon antagonist-mediated internalization: a useful approach to study glucagon receptor pharmacology.
Adv Exp Med Biol. 2009; 611:325-326

PMID: 19400212 [PubMed - indexed for MEDLINE]

9)
Ye, S., Köhrer, C., Huber, T., Kazmi, M., Sachdev, P., Yan E.C., Aditi Bhagat, RajBhandary, U.L., & Sakmar T.P.
Site-specific incorporation of keto amino acids into functional G protein-coupled receptors using unnatural amino acid mutagenesis.
J Biol Chem2007; 283(3):1525-1533

PMID: 17993461 [PubMed - indexed for MEDLINE]

8)
Sachdev, P.,Menon, S., Kastner, D.B., Chuang, J.Z., Yeh, T.Y., Conde, C., Caceres, A., Sung, C.H. & Sakmar, T.P.
G protein betagamma subunit interaction with the dynein light-chain component Tctex-1 regulates neurite outgrowth.
The EMBO Journal 2007; 26:2621–2632

PMID: 17491591 [PubMed - indexed for MEDLINE]

7)
Sachdev, P., Zeng, L. and Wang, L.-H.
Distinct role of phosphatidylinositol 3-kinase in Vav3-mediated cell transformation, cell motility and cell morphology changes.
J. Biol. Chem. 2002; 277: 17638-17648

PMID: 11884391 [PubMed - indexed for MEDLINE]

6)
Nguyen, K.T., Zong, C.S., Uttamsingh, S., Sachdev, P., Bhanot, M., Le, M.T., Chan, J.L., and Wang, L.-H.
The role of phosphatidylinositol 3-kinase, Rho family GTPases, and Stat3 in Ros-induced transformation.
J. Biol. Chem. 2002; 277: 11107-11115.

PMID: 11799110 [PubMed - indexed for MEDLINE]

5)
Sachdev, P., Jiang, Y, Li W., Miki, T., Maruta, H., Nur-E-Kamal, M.S.A., Wang, LH. (2001).
Differential requirement for Rho family GTPases in an oncogenic IGF-1 receptor-induced cell transformation.
J. Biol. Chem. 2001; 276: 26461-26471

PMID: 11346642 [PubMed - indexed for MEDLINE]

4)
Zeng, L., Sachdev, P., Yan, L., Chan, J., Trenkle, T., McClelland, M., Welsh, J., and Wang, LH. (2000).
Vav3 mediates receptor protein tyrosine kinase signaling, regulates GTPase activity, modulates cell morphology, and induces cell transformation.
Mol. Cell Biol. 2000; 20: 9212-9224

PMID: 11094073 [PubMed - indexed for MEDLINE]

MANUSCRIPTS SUBMITTED AND IN PREPARATION

3)
Kapoor, N., Menon S.T., Chauhan, R., Sachdev, P., and Sakmar, T.P.
Structural Evidence for a Sequential Release Mechanism for Activation of Heterotrimeric G Proteins.
Manuscript submitted Journal of Molecular Biology

2)
Decaillot, F., Kazmi, M., Sakmar, T.P., and Sachdev, P.
CXCR7/CXCR4 heterodimer constitutively recruits b-arrestin to enhance cell migration.
Manuscript in preparation

1)
Banerjee S., Sachdev, P., Grunbeck A., Huber T., and Sakmar T.P.
Efficient microincorporation of human CCR5 into nanoscale discoidal lipid particles.
Manuscript in preparation

Posters

5)
Banerjee, S., Grunbeck, A., Huber, T., Sachdev, P., and Sakmar T.P.
Rapid Incorporation of Heterologously Expressed GPCR CCR5 in Nanoscale Apolipoprotein Bound Bilayers (NABBs).
The 53rd Annual Biophysical Society Meeting
February 28 - March 4, 2009. Boston, MA.

4)
Sachdev, P., Menon, S., Yeh., T.Y., Conde, C., Caceres, A., Sung, C.H., and Sakmar, T.P.
Role of G protein bg subunit and dynein light chain Tctex-1 in neuronal differentiation
Rockefeller University Postdoctoral Retreat
September 22, 2007. New York, NY.

3)
Sachdev, P., Sung, CH and Sakmar, TP.
Role of Gbg and Tctex-1 in neurite outgrowth and neuronal differentiation of primary hippocampal neurons.
The 46th American Society for Cell Biology Annual Meeting
December 9-13, 2006.San Deigo, CA.

2)
Sachdev, P., Sung, C.H. and Sakmar, T.P.
Heterotrimeric G Protein bg Subunits Interact with the Cytoplasmic Dynein Light Chain Tctex-1.
The 43rd American Society for Cell Biology Annual Meeting,
December 13-17, 2003.San Francisco, CA.

1)
Sachdev, P., Zeng, L., and Wang, L.H. (2001).
Distinct role of PI3 kinase in Vav3-mediated cell transformation versus cell morphology changes.
Invited oral presentation at the 17th Annual meeting on Oncogenes: Cancer Cell Signal Transduction, Frederick, MD.

The Sakmar Laboratory

The Laboratory of
Molecular Biology & Biochemistry
at Rockefeller University

Thomas P. Sakmar

Head of Laboratory

Laboratory of Molecular Biology and Biochemistry

Rockefeller Research Building 510

The Rockefeller University, Box 187
1230 York Avenue
New York, NY 10065

Telephone: 212-327-8288
Fax: 212-327-7904
sakmar@rockefeller.edu

Biosketch

Education
Research
Awards
Professional Orgainzations
Scientific Review Activities
External Reviewer(1991-present)
Peer Review Panels-Study Sections
Other Review-Advisory Panels
Consulting Activities (Industry)
Non-Profit, Educational & Governmental
Board Memberships (Non-Profit Organizations)
Named Lectureships-Plenary & Keynote Lectures
Published Papers

The Sakmar Laboratory

The Laboratory of
Molecular Biology & Biochemistry
at Rockefeller University

Education

1985 – 1988
Postdoctoral Fellow, Departments of Biology & Chemistry, Laboratory of Prof. H. G. Khorana, Massachusetts Institute of Technology, Cambridge, MA

1985 – 1990
Graduate Assistant in Medicine, Massachusetts General Hospital, Boston, MA

1982 – 1985
Clinical Fellow in Medicine (J. T. Potts, Jr., Chairman), Harvard Medical School, Boston, MA

1983 – 1985
Resident in Medicine, Massachusetts General Hospital, Boston, MA

1982 – 1983
Intern in Medicine, Massachusetts General Hospital, Boston, MA

1982
M.D. with Honors, University of Chicago, Pritzker School of Medicine

1979 – 1980
Research Student, Laboratories of R. L. Heinrikson & P. B. Sigler, Department of Biochemistry, University of Chicago, Chicago, IL

1977 – 1978
Research Student, Laboratories of J. D. Robbins & D. T. Liu, Biochemistry and Biophysics Branch, Bureau of Biologics, Food and Drug Administration, Bethesda, MD

1978
A.B. with General Honors (Chemistry), The College at the University of Chicago, Chicago, IL

The Sakmar Laboratory

The Laboratory of
Molecular Biology & Biochemistry
at Rockefeller University

Research

Thomas Sakmar, a biochemist and physician, heads the Laboratory of Molecular Biology and Biochemistry at The Rockefeller University. Dr. Sakmar uses interdisciplinary approaches to study how chemical signals are relayed from the outside to the inside of a cell. This process, known as transmembrane signaling, allows cells and organisms to sense their environments. Much of Dr. Sakmar’s research focuses on vision and on the signaling molecules in the retina, with implications for understanding retinitis pigmentosa, macular degeneration, night blindness, color blindness, and other vision disorders. Investigations in the Sakmar laboratory also explore signaling pathways that play a role in taste perception, glucose metabolism, the brain’s response to the neurotransmitter dopamine, and the ability of the AIDS virus to enter human cells.

Dr. Sakmar received a B.A. in chemistry in 1978 from the University of Chicago and went on to earn an M.D. in 1982 from Chicago’s Pritzker School of Medicine. He was an intern and resident in internal medicine at Massachusetts General Hospital and a clinical fellow at Harvard Medical School. In 1985, Dr. Sakmar began postdoctoral research with Nobel laureate H. Gobind Khorana in the departments of biology and chemistry at the Massachusetts Institute of Technology. He remained at M.I.T. until 1990, when he moved to Rockefeller as an assistant professor and laboratory head. Dr. Sakmar became a tenured professor in 1998 and the University’s Richard M. and Isabel P. Furlaud Professor in 2002. In addition, from 1991 to 2004 he was associated with the Howard Hughes Medical Institute. From February 2002 through August 2003, Dr. Sakmar served as acting president of The Rockefeller University.

The Sakmar Laboratory

The Laboratory of
Molecular Biology & Biochemistry
at Rockefeller University

Awards

•NATO Advanced Study Fellowship, NATO Advanced Study Institute on Membrane Biophysics & Intercellular Communication, Les Houches, France (1979)
•Alpha Omega Alpha () Medical Honor Society (1982);
•National Research Service Award, National Institutes of Health, NEI (1986-1988);
•American Society for Photobiology (ASP), New Investigator Award (1995);
•Ellison Foundation Senior Scholar Award (2001);
I•nterviewed by Nature Drug Discovery as one of the 20 world’s leading experts on GPCR research (Nat Revs Drug Disc 3:575-626, 2004)

The Sakmar Laboratory

The Laboratory of
Molecular Biology & Biochemistry
at Rockefeller University

Professional Organizations

•American Association for the Advancement of Science (AAAS)
•American Chemical Society (ACS)
•Association for Chemoreception Sciences (AChemS)
•American Medical Association (AMA)
•American Society for Biochemistry & Molecular Biology (ASBMB)
•American Society for Photobiology (ASP)
•American Society of Tropical Medicine and Hygiene
•Association for Research in Vision & Ophthalmology (ARVO)
•Biophysical Society
•The Harvey Society
•International Society for Eye Research (ISER)
•Massachusetts Medical Society
•New York Academy of Sciences
•The Practitioners’ Society of New York
•The Protein Society
•Society of General Physiologists

The Sakmar Laboratory

The Laboratory of
Molecular Biology & Biochemistry
at Rockefeller University

Scientific Review Activities

•Editorial Board – Journal of General Physiology (1995–present); Journal of Biological Chemistry (2009–2014)
•Journal Referee – (ongoing)
•American Journal of Physiology
•Biochemical Journal
•Biochemistry
•Biochimica et Biophysica Acta
•Bioorganic & Medicinal Chemistry
•Biophysical Journal
•Cellular & Molecular Life Sciences
•Chemical Reviews
•Chemical Senses
•Chemistry & Biology
•Current Opinions in Chemical Biology
•Diabetes
•EMBO Journal
•Endocrinology
•European Journal of Biochemistry
•Experimental Eye Research
•FEBS Journal
•FEBS Letters
•Gene
•Journal of the American Chemical Society
•Journal of Biological Chemistry
•Journal of Clinical Investigation
•Journal of Experimental Medicine
•Journal of General Physiology
•Journal of Molecular Biology
•Journal of Molecular Modeling
•Journal of Neuroscience
•Journal of Pharmacology & Experimental Therapeutics
•Journal of Photochemistry and Photobiology
•Journal of Physical Chemistry
•Journal of Respiratory Cell &Molecular Biology
•Journal of Virology
•Life Sciences
•Metabolism: Clinical & Experimental
•Metabolism: Clinical & Therapeutic
•Molecular Biology & Evolution
•Molecular Cell
•Nature
•Nature Biotechnology
•Nature Genetics
•New England Journal of Medicine
•Photochemistry & Photobiology
•PLoS Biology
•Proceedings of the National Academy of Sciences U.S.A.
•Proceedings of the Royal Academy London B
•Protein Expression & Purification
•Proteins: Structure, Function & Bioinformatics
•Science
•Structure
•The Hastings Center Report
•Trends in Biochemical Sciences
•Trends in Pharmacological Sciences
•Visual Neuroscience

The Sakmar Laboratory

The Laboratory of
Molecular Biology & Biochemistry
at Rockefeller University

External Reviewer - (1991 – present)

•Austrian Science Fund (FWF)
•Cottrell College Science Award Program
•Department of the Army, Biochemistry & Neuroscience Research Branch
•HHMI, International Grants Program
•International Human Frontier Science Program
•Kentucky Science and Engineering Foundation
•Manitoba Health Research Council
•MRC Council’s Triage: Molecular & Cellular Medicine Board (t-MCMB)
•Netherlands Organization for Scientific Research (NWO)
•NSF Biophysics Program
•NSF/Experimental Program to Stimulate Competitive Research (EPSCoR), Infrastructure Improvement Program, North Dakota
•NSF Molecular Biochemistry Program
•NSF Molecular Biology Program
•NSF Neuroscience Program
•NSF Sensory Systems Program
•United States-Israel Binational Science Foundation
•The Washington Advisory Group, L.L.C.
•The Wellcome Trust

The Sakmar Laboratory

The Laboratory of
Molecular Biology & Biochemistry
at Rockefeller University

Peer Review Panels-Study Sections

•NIH Visual Sciences Study Section, ad hoc Reviewer (1992)
• NIH Visual Sciences C Study Section, Special Reviewer (1995, 1996)
• NIH Visual Sciences C Study Section, Special Reviewer (1998)
• NIH Molecular, Cellular & Development Neuroscience Study Section – 3, Special Reviewer (1999)
• NIH Endocrinology Study Section, Special Reviewer (1999)
• NIH Pharmacology Study Section, Special Reviewer (2000)
• NIH BRT-A Review Committee, ad hoc Reviewer & Site Visitor (2000)
• NIH Visual Sciences C Study Section, Special Reviewer (2001)
• American Heart Association NEA5B Study Section (2005)
• NIH NIDDKD Board of Scientific Counselors, ad hoc Member (2005)
• NIH BDPE Study Section, ad hoc Reviewer (2005, 2006)
• NIH NIDCD Board of Scientific Counselors, ad hoc Member (2008)

The Sakmar Laboratory

The Laboratory of
Molecular Biology & Biochemistry
at Rockefeller University

Other Review-Advisory Panels

•Industrial Advisory Board, NSF/Experimental Program to Stimulate Competitive Research (EPSCoR), Interdisciplinary Program in Signal Transduction, Medical University of South Carolina (1997)

•HHMI Research Training Fellowships for Medical Students Program (2001 – 2003)
•Radcliffe Institute for Advanced Study Advisory Committee (2003 – present)
•External Advisory Committee for the Center of Biomedical Research Excellence (COBRE) on Membrane Protein Production and Characterization (COMPPAC), NCRR/NIH Institutional Development Award Program, University of Delaware (2006 – present)
•Tri-Institutional Embryonic Stem Cell Initiative ESCRO Committee (2008 – present)

The Sakmar Laboratory

The Laboratory of
Molecular Biology & Biochemistry
at Rockefeller University

Consulting Activities (Industry)

•Consultant, Merck & Co., Rahway, NJ (1996)
•Consultant, LeukoSite, Inc., Cambridge, MA (1998)
•Scientific Advisory Board, LeukoSite, Inc., Cambridge, MA (1998 – 1999)
•Consultant, Schering-Plough Research Institute, Kenilworth, NJ (1999 – 2001)
•Scientific Advisory Board (Founding Member), Natural Pharmaceuticals, Inc., Beverly, MA (1999 – present)
•Consultant, Millennium Pharmaceuticals, Inc., Cambridge, MA (2000 – 2003)
•Consultant, Merck & Co., Rahway, NJ (2001)
•Consultant, Progenics Pharmaceuticals, Inc., Tarrytown, NY (2001 – 2003)
•MVM Life Science Partners, Boston, MA (2004)
•Scientific Advisory Board, NIH-U19 Program Project, Progenics Pharmaceuticals, Inc., Tarrytown, NY (2006 – present)
•Scientific Advisory Board (Founding Member), Resolvyx Pharmaceuticals, Inc. , Boston, MA (2006 – present)
•Scientific Advisory Board (Founding Member), Ascent Pharmaceuticals Inc., Boston, MA (2007 – present)

The Sakmar Laboratory

The Laboratory of
Molecular Biology & Biochemistry
at Rockefeller University

Consulting Activities (Non-Profit, Educational and Governmental Organizations)

•Physician Consultant, Rockefeller University Occupational Health Office (1997 – 2002, 2003 – present)
•Consultant, “The Genomic Revolution” Exhibition, American Museum of Natural History, New York, NY (2001)
•Dolan DNA Learning Center, Cold Spring Harbor Laboratory, NY (2001); Georgetown University Medical Center (2004 – 2006)
•United States Court of Appeals for the Second Circuit, Federal Bar Council American Inn of Court, Stem Cell Biology, Policy and Ethics, New York, NY (2007)

The Sakmar Laboratory

The Laboratory of
Molecular Biology & Biochemistry
at Rockefeller University

Board Memberships (Non-profit Organizations):

•Trustee, Aaron Diamond AIDS Research Center, New York, NY (2002 – 2003)
•Member of the Governing Council, Rockefeller Archive Center, Sleepy Hollow, NY (2002 – 2003)
•Trustee, Rockefeller University Board of Trustees, New York, NY (2002 – 2003)
•Trustee, Academic Medical Development Corporation (AmDec), New York, NY (2002 - 2003)
•Trustee, Helen Hay Whitney Foundation (2003 – present)
•Director, The Medical Letter (2004 – present)

The Sakmar Laboratory

The Laboratory of
Molecular Biology & Biochemistry
at Rockefeller University

Named Lectureships / Plenary Lectures / Keynote Lectures

•May 1995 Sonderforschungsbereich Lecture, Albert-Ludwigs-Universität, Freiburg, Germany
•June 1995 New Investigator Award Lecture, American Society for Photobiology, 23rd Annual Meeting, Washington, DC
•March 1999 Dr. George W. Raiziss Biochemical Rounds, Department of Biochemistry & Biophysics, University of Pennsylvania, Philadelphia, PA
•May 1999 Sonderforschungsbereich Lecture, Zelluläre Funktionen dynamisher Proteinwechselwirkengen, Albert-Ludwigs-Universität, Freiburg, Germany
•October 2000 Merck Frosst Lecture, Great Lakes GPCR Symposium, London, Ontario, Canada
•December 2001 Alfred E. Mirsky Christmas Lectures, Rockefeller University, New York, NY
•April 2004 G-Protein Signaling Workshop - 2004, New York, NY
•May 2005 Medicinal Chemistry Symposium, American Chemical Society Regional Meeting, Piscataway, NJ
•May 2005 Allosteric Modulation of G Protein-Coupled Receptors Symposium, New York Academy of Sciences, New York, NY
•October 2006 11th International G-Protein Coupled Receptor Conference, IBC USA Symposium, Las Vegas, NV
•March 2007 Rhodopsin and the G Protein Activation Cascade: a Special Journey with and for Marc Chabre, Nice, France
•September 2007 Screening Targets Conference & Exhibition, SelectBiosciences Symposium, Boston, MA
•November 2008 Section Days of the Life Sciences, Ruhr-University, Bochum, Germany
•October 2009 Great Lakes GPCR Symposium, Rochester, NY

The Sakmar Laboratory

The Laboratory of
Molecular Biology & Biochemistry
at Rockefeller University

Published Papers

146).
Miller, J., Agarwal, A., Devi, L. A., Fontanini, K., Hamilton, J. A., Pin, J. P., Shields, D. C., Spek, C. A.,Sakmar, T. P., Kuliopulos, A. & Hunt, S. W., 3rd.
Insider Access: Pepducin Symposium Explores a New Apprach to GPCR Modulation.
Ann N Y Acad Sci 1180:E1–E12 (2009).

145).
Ahuja, S., Eilers, M., Hirshfeld, A., Yan, E. C. –Y., Ziliox, M., Sakmar, T. P., Sheves, M. & Smith, S. O.
6-s-cis Conformation and Polar Binding Pocket of the Retinal Chromophore in the Photoactivated State of Rhodopsin.
J Am Chem Soc 131:15160–15169 (2009).

144).
Kapoor, N., Menon, S. T., Chauhan, R., Sachdev, P., & Sakmar, T. P.
Structural Evidence for a Sequential Release Mechanism for Activation of Heterotrimeric G Proteins.
J Mol Biol 393:882–897 (2009).

143).
Ye, S., Huber, T., Vogel, R. & Sakmar, T. P.

FTIR Analysis of GPCR Activation using Azido Probes

Nat Chem Biol 5:397–399 (2009).

PMID: 19396177 [PubMed - indexed for MEDLINE]

142).
142 Ahuja, S., Hornak, V., Yan, E. C. Y., Syrett, N., Goncalves, J. A., Hirshfeld, A., Ziliox, M., Sakmar, T. P., Sheves, M., Reeves, P. J., Smith, S. O. & Eilers, M.

Helix Movement Is Coupled to Displacement of the Second Extracellular Loop in Rhodopsin Activation.

Nat Struct Mol Biol 16:168–175 (2009).

MID: 19182802 [PubMed - indexed for MEDLINE]

141).
Sakmar, T. P. & Huber, T.
Rhodopsin.
in Encyclopedia of Neuroscience. (Squire, L.R., ed.) Oxford: Academic Press. 8:365–372 (2009).

[not indexed for MEDLINE]

140).
Sakmar, T. P.

Structure and Function of G Protein-Coupled Receptors: Lessons from Recent Crystal Structures.

in Handbook of Cell Signaling, 2nd edition. (Bradshaw, R. A. & Dennis, E. A., eds.) Oxford: Academic Press. pp. 151–156 (2009).

139).
Seibert, C., Veldkamp, C.T., Peterson, F.C., Chait, B.T., Volkman, B.F. &Sakmar, T. P.

Sequential Tyrosine Sulfation of CXCR4 by Tyrosylprotein Sulfotransferases.

Biochemistry 47:11251–11262 (2008). [*Ranked 19th Most Downloaded Article in Biochemistry Dec. 2008]

PMID: 18834145 [PubMed - indexed for MEDLINE]

138).
Huber, T., Menon, S. & Sakmar, T. P.

Structural Basis for Ligand Binding and Specificity in Adrenergic Receptors: Implications for GPCR-Targeted Drug Discovery.

Biochemistry 47:11013–11023 (2008).
[*Ranked Most Downloaded Article in Biochemistry Oct. – Dec. 2008; 10th Most Downloaded for past 12 months, Feb. – Mar. 2009; 16th Most Downloaded for past 12 months April – May 2009]

PMID: 18821775 [PubMed - indexed for MEDLINE]

137).
cover137 Veldkamp, C. T., Seibert, C., Peterson, F. C., De la Cruz, N. B., Haugner, III, J. C., Basnet, H., Sakmar, T. P. & Volkman, B. F.

Structural Basis of CXCR4 Sulfotyrosine Recognition by the Chemokine SDF-1/CXCL12.

Sci Signal 1:ra4 (2008). [*Cover Article]

PMID: 18799424 [PubMed - indexed for MEDLINE]

136).
136 Vogel, R., Mahalingam, M., Lüdeke, S., Huber, T., Siebert, F. & Sakmar, T. P.

Functional Role of the “Ionic Lock” – an Interhelical Hydrogen-bond Network in Family A Heptahelical Receptors.

J Mol Biol 380:648–655 (2008).

PMID: 18554610 [PubMed - indexed for MEDLINE]

135).
Huber, T. & Sakmar, T. P.

Rhodopsin’s Active State Is Frozen Like a DEER in the Headlights.

Proc Natl Acad Sci U S A 105:7343–7344 (2008).

PMID: 18492801 [PubMed - indexed for MEDLINE]

134).
136 Banerjee, S., Huber, T. & Sakmar, T. P.

Rapid Incorporation of Functional Rhodopsin into Nanoscale Apolipoprotein Bound Bilayers (NABB) Particles.

J Mol Biol 377:1067–1081 (2008).

PMID: 18313692 [PubMed - indexed for MEDLINE]

133).
133 Louis, M., Huber, T., Benton, R., Sakmar, T. P. & Vosshall, L. B.

Bilateral Olfactory Senstory Input Enhances Chemotaxis Behavior.

Nat Neurosci 11:187–199 (2008).

PMID: 18157126 [PubMed - indexed for MEDLINE]

132).
136 Ye, S., Köhrer, C., Huber, T., Kazmi, M., Sachdev, P., Yan, E. C. Y., Bhagat, A., Rajbhandary, U. L. & Sakmar, T. P.

Site-specific Incorporation of Keto Amino Acids into Functional G Protein-coupled Receptors Using Unnatural Amino Acid Mutagenesis.

J Biol Chem 283:1525–1533 (2008).

PMID: 17993461 [PubMed - indexed for MEDLINE]

131).
Seibert, C. & Sakmar, T. P.

Toward a Framework for Sulfoproteiomics: Synthesis and Characterization of Sulfotyrosine-containing Peptides.

Biopolymers 90:459–477 (2008).

PMID: 17680702 [PubMed - indexed for MEDLINE]

130).
Janz, J. M., Sakmar, T. P. & Min, K. C.

A Novel Interaction Between AIP4 and bPIX Is Mediated by an SH3 Domain.

J Biol Chem 282:28893–28903 (2007).

PMID: 17652093 [PubMed - indexed for MEDLINE]

129).
129 Periole, X., Huber, T., Marrink, S. J. & Sakmar, T. P.

G Protein-coupled Receptors Self-assemble in Dynamics Simulations of Model Bilayers.

J Am Chem Soc 129:10126–10132 (2007).

PMID: 17658882 [PubMed - indexed for MEDLINE]

128).
128 Sachdev, P., Menon, S., Kastner, D. B., Chuang, J. Z., Yeh, T. Y., Conde, C., Caceres, A., Sung, C. H. & Sakmar, T. P.

G Protein bg Sununit Interaction with the Dynein Light-Chain Component Tctex-1 Regulates Neurite Outgrowth.

EMBO J 26:2621–2632 (2007).

PMID: 17491591 [PubMed - indexed for MEDLINE]

127).
Yan, E. C. Y., Epps., J., Lewis, J. W.Szundi, I., Bhagat, A., Sakmar, T. P. & Kliger, D. S.

Photointermediates of the Rhodopsin S186A Mutant As a Probe of the Hydrogen Bond Network in the Chromophore Pocket and the Mechanism of Counterion Switch.

J Phys Chem C 111:8843–8848 (2007).
[not indexed for MEDLINE]

126).
126 Vogel, R., Sakmar, T. P., Sheves, M. & Siebert, F.

Coupling of Protonation Switches During Rhodopsin Activation.

Photochem Photobiol 83:286–292 (2007).

PMID: 17576345 [PubMed - indexed for MEDLINE]

125).
125 Botelho, A. V., Huber, T., Peterson, F. C., Sakmar, T. P. & Brown, M. F.

Curvature and Hydrophobic Forces Drive Oligomerization and Modulate Activity of Rhodopsin in Membranes.

Biophys J 91:4464–4477 (2006).

PMID: 17012328 [PubMed - indexed for MEDLINE]

124).
Sakmar, T. P.

Timing is Everything: Direct Measurement of Retinol Production in Cones and Rods.

J Gen Physiol 128:147–148 (2006).

PMID: 16847095 [PubMed - indexed for MEDLINE]

123).
123 Vogel, R., Siebert, F., Yan, E. C. Y., Sakmar, T. P., Hirshfeld, A. & Sheves, M.

Modulating Rhodopsin Receptor Activation by Altering the pKA of the Retinal Schiff Base.
J Am Chem Soc 128:10530–10512 (2006).

PMID: 16895417 [PubMed - indexed for MEDLINE]

122).
122 Veldkamp, C. T., Seibert, C., Peterson, F. C., Sakmar, T. P. & Volkman, B. F.

Recognition of a CXCR4 Sulfotyrosine by the Chemokine Stromal Cell-derived Factor-1a (SDF-1a/CXCL12).

J Mol Biol 359:1400–1409 (2006).

PMID: 16725153 [PubMed - indexed for MEDLINE]

121).
121 Lewis, J. W., Szundi, I., Kazmi, M. A., Sakmar, T. P. & Kliger, D. S.

Proton Movement and Photointermediate Kinetics in Rhodopsin Mutants.

Biochemistry 45:5430–5439 (2006).

PMID: 16634624 [PubMed - indexed for MEDLINE]

120).
120 Kazmi, M., Sakmar, T. P. & Yau, K. –W.

Parietal-Eye Phototransduction Components: Insight into Vertebrate Photoreceptor Evolution.

Science 311:1617–1621 (2006).

PMID: 16543463 [PubMed - indexed for MEDLINE]

119).
Hoelz, A., Janz, J. M., Lawrie, S. D., Corwin, B., Lee, A. & Sakmar, T. P.

Crystal Structure of the SH3 Domain of bPIX in Complex with a High Affinity Peptide from PAK2.

J Mol Biol 358:509–522 (2006).

PMID: 16527308 [PubMed - indexed for MEDLINE]

118).
118 Seibert, C., Ying, W., Gavrilov, S., Tsamis, F., Kuhmann, S. E., Palani, A., Tagat, J. R., Clader, J. W., McCombie, S. W., Baroudy, B. M., Smith, S. O., Dragic, T., Moore, J. P. & Sakmar, T. P.

Interaction of Small Molecule Inhibitors of HIV-1 Entry with CCR5.

Virology 349:41–54 (2006).

PMID: 16494916 [PubMed - indexed for MEDLINE]

117).
117 Vogel, R., Ludeke, S., Siebert, F., Sakmar, T. P., Hirshfeld, A. & Sheves, M.

Agonists and Partial Agonists of Rhodopsin: Retinal Polyene Methylation Affects Receptor Activation.

Biochemistry 45:1640–1652 (2006).

PMID: 16460011 [PubMed - indexed for MEDLINE]

116).
119 Ludeke, S., Beck, M., Yan, E. C., Sakmar, T. P., Siebert, F. & Vogel, R.

The Role of Glu181 in the Photoactivation of Rhodopsin.

J Mol Biol 353:345–356 (2005).

PMID: 16169009 [PubMed - indexed for MEDLINE]

115).
Huber, T. & Sakmar, T. P.

The Photoreceptor Membrane As a Model System in the Study of Biological Signal Transduction.

in Advances in Planar Lipid Bilayers and Liposomes. (Tien, H. T. & Ottova, A., eds.) Elsevier, Oxford, pp. 182–206 (2005).

[not indexed for MEDLINE]

114).
Sakmar, T. P.

Twenty Years of the Magnificent Seven.

The Scientist 19:22-23 (2005). [*Cover Article]

113).
Bartfai, T., Benovic, J. L., Bockaert, J., Bond, R. A., Bouvier, M., Christopoulos, A., Civelli, O., Devi, L. A., George, S. R., Inui, A., Kobilka, B., Leurs, R., Neubig, R., Pin, J. –P., Quirion, R., Roques, B. P., Sakmar, T. P., Seifert, R., Stenkamp, R. E. & Strange, P. G.
Twenty Questions: The State of GPCR Research in 2004.

Nat Revs Drug Disc 3:575–626 (2004).

[not indexed for MEDLINE]

112).
Yan, E. C., Ganim, Z., Kazmi, M. A., Chang, B. S. W., Sakmar, T. P. & Mathies, R. A.

Resonance Raman Analysis of the Mechanism of Energy Storage and Chromophore Distortion in the Primary Visual Photoproduct.

Biochemistry 43:10867–10876 (2004).

PMID: 15323547 [PubMed - indexed for MEDLINE]

111).
111 Lewis, J. W., Szundi, I., Kazmi, M. A., Sakmar, T. P. & Kliger, D. S.

Time-Resolved Photointermediate Changes in Rhodopsin Glu181 Mutants.

Biochemistry 43:12614–12621 (2004).

PMID: 15449951 [PubMed - indexed for MEDLINE]

110).
110 Billick, E., Seibert, C., Pugach, P., Ketas, T., Trkola, A., Endres, M. J., Murgolo, N. J., Coates, E., Reyes, G. R., Baroudy, B. M., Sakmar, T. P., Moore, J. P. & Kuhmann, S. E.

The Differential Sensitivity of Human and Rhesus Macaque CCR5 to Small-Molecule Inhibitors of Human Immunodeficiency Virus Type 1 Entry Is Explained by a Single Amino Acid Difference and Suggests a Mechanism of Action for These Inhibitors.

J Virol 78:4134–4144 (2004).

PMID: 15047829 [PubMed - indexed for MEDLINE]

109).
109 Seibert, C., & Sakmar, T. P.

Small-Molecule Antagonists of CCR5 and CXCR4: A Promising New Class of Anti-HIV-1 Drugs.

Curr Pharm Design 10:2041–2062 (2004).

PMID: 15279544 [PubMed - indexed for MEDLINE]

108).
Sakmar, T. P.

Rhodopsin.

in Encyclopedia of Neuroscience. 3rd Ed. (Adelman, G. & Smith, B. H., eds.) Elsevier Science B.V., Amsterdam, Holland (2004).

[not indexed for MEDLINE]

107).
Sakmar, T. P.

Structure and Function of G Protein-Coupled Receptors: Lessons from the Crystal Structure of Rhodopsin.

in Handbook of Cell Signaling, Academic Press, San Diego, CA, pp. 139–143 (2003).

[not indexed for MEDLINE]

106).
Yan, E. C., Kazmi, M. A., Ganim, Z., Hou, J. M., Pan, D., Chang, B. S. W., Sakmar, T. P. & Mathies, R. A.

Retinal Counterion Switch in the Photoactivation of the G Protein-Coupled Receptor Rhodopsin.

Proc Natl Acad Sci U S A 100:9262–9267 (2003).

[*See commentary: Birge, R. R. & Knox, B. E. Perspectives on the Counterion Switch-Induced Photoactivation of the G Protein-Coupled Receptor Rhodopsin. Proc Natl Acad Sci U S A 100:9105–9107 (2003).]

PMID: 12835420 [PubMed - indexed for MEDLINE]

105).
105 Tsamis, F., Gavrilov, S., Kajumo, F., Seibert, C., Kuhmann, S., Ketas, T., Trkola, A., Palani, A., Clader, J. W., Tagat, J. R., McCombie, S., Baroudy,B., Moore, J. P., Sakmar, T. P. & Dragic, T.

Analysis of the Mechanism by Which the Small-Molecule CCR5 Antagonists SCH-351125 and SCH-350581 Inhibit Human Immunodeficiency Virus Type 1 Entry.

J Virol 77:5201–5208 (2003).

PMID: 12692222 [PubMed - indexed for MEDLINE]

104).
Sakmar, T. P.

Color Vision.

in Adler's Physiology of the Eye, 10th Edition. (Kaufmann, P. L. & Alm, A., eds.)
Mosby, St. Louis, pp. 578–585 (2003).

[not indexed for MEDLINE]

103).
Seibert, C., Cadene, M., Sanfiz, A., Chait, B. T. & Sakmar, T. P.

Tyrosine Sulfation of CCR5 N-Terminal Peptide by Tyrosylprotein Sulfotransferases 1 and 2 Follows a Discrete Pattern and Temporal Sequence.

Proc Natl Acad Sci U S A 99:11031–11036 (2002).

PMID: 12169668 [PubMed - indexed for MEDLINE]

102).
Unson, C. G., Wu, C. –R., Yoo, B., Cheung, C., Jiang, Y., Sakmar, T. P. & Merrifield, R. B.

The Roles of Specific Extracellular Domains of the Glucagon Receptor in Ligand Binding and Signaling.

Biochemistry 41:11795–11803 (2002).

PMID: 12269822 [PubMed - indexed for MEDLINE]

101).
De, S. & Sakmar, T. P.

Interaction of A2E with Model Membranes. Implications to the Pathogenesis of Age-Related Macular Degeneration.

J Gen Physiol 120:147–157 (2002).

PMID: 12149277 [PubMed - indexed for MEDLINE]

100).
100 Gopala Krishna, A., Menon, S. T., Terry, T. J.& Sakmar, T. P.

Evidence That Helix 8 of Rhodopsin Acts As a Membrane-Dependent Conformational Switch.

Biochemistry 41:8298–8309 (2002).

PMID: 12081478 [PubMed - indexed for MEDLINE]

99).
Chang, B. S. W., Jönsson, K., Kazmi, M. A., Donoghue, M. J. & Sakmar, T. P.

Recreating a Functional Ancestral Archosaur Visual Pigment.

Mol Biol Evol 19:1483–1489 (2002). [*Rated “EXCEPTIONAL” by the Faculty of 1000]

PMID: 12200476 [PubMed - indexed for MEDLINE]

98).
Marin, E. P., Gopala Krishna, A. & Sakmar, T. P.

Disruption of the a5 Helix of Transducin Impairs Rhodopsin-Catalyzed Nucleotide Exchange.

Biochemistry 41:6988–6994 (2002).

PMID: 12033931 [PubMed - indexed for MEDLINE]

97).
Yan, E. C. Y., Kazmi, M. A., De, S., Chang, B. S. W., Seibert, C., Marin, E. P., Mathies, R. A. & Sakmar, T. P.

Function of Extracellular Loop 2 in Rhodopsin: Glutamic Acid 181 Modulates Stability and Absorption Wavelength of Metarhodopsin II.

Biochemistry 41:3620–3627 (2002).

PMID: 11888278 [PubMed - indexed for MEDLINE]

96).
Sakmar, T. P.

The Structure of Rhodopsin and the Superfamily of Seven-Helical Receptors: The Same and Not the Same.

Curr Opin Cell Biol 14:189–195 (2002).

PMID: 11891118 [PubMed - indexed for MEDLINE]

95).
Sakmar, T. P., Menon, S. T., Marin, E. P. & Awad, E. S.

Rhodopsin: Insights from Recent Structural and Mutagenesis Studies.

Annu Rev Biophys Biomol Struct 31:443–484 (2002).

PMID: 11988478 [PubMed - indexed for MEDLINE]

94).
Chang, B. S. W., Kazmi, M. & Sakmar, T. P.

Synthetic Gene Technology: Applications to Ancestral Gene Reconstruction and Structure-Function Studies of Receptors.

Methods Enzymol 343:274–294 (2002).

PMID: 11665573 [PubMed - indexed for MEDLINE]

93).
Jiang, Y., Cypess, A. M., Muse, E. D., Wu, C-. R., Unson, C. G., Merrifield, R. B. & Sakmar, T. P.

Glucagon Receptor Activates Extracellular Signal-Regulated Protein Kinase (ERK) 1/2 via cAMP-Dependent Protein Kinase.

Proc Natl Acad Sci U S A 98:10102–10107 (2001).

PMID: 11517300 [PubMed - indexed for MEDLINE]

92).
Menon, S. T., Han, M. & Sakmar, T. P.

Rhodopsin: Structural Basis of Molecular Physiology.

Physiol Revs 81:1659–1688 (2001). [*Cover Article]

PMID: 11581499 [PubMed - indexed for MEDLINE]

91).
Marin, E. P., Krishna, A. G. & Sakmar, T. P.

Rapid Activation of Transducin by Mutations Distant From the Nucleotide-Binding Site: Evidence for a Mechanistic Model of Receptor-Catalyzed Nucleotide Exchange by G Proteins.

J Biol Chem 276:27400–27405 (2001).

PMID: 11356823 [PubMed - indexed for MEDLINE]

90).
Marin, E. P., Krishna, A. G., Archambault, V., Simuni, E., Fu, W. Y. & Sakmar, T. P.

The Function of Interdomain Interactions in Controlling Nucleotide Exchange Rates in Transducin.

J Biol Chem 276:23873–23880 (2001).

PMID: 11290746 [PubMed - indexed for MEDLINE]

89).
Cypess, A. M., Muse, E. D., Wu, C-. R., Unson, C. G. & Sakmar, T. P.

Glucagon Receptor Causes Glucagon-Dependent Activation of Erk 1/2 in H22 Stable Cell Lines.

in Peptides for the New Millennium. (Fields, G. B., Barany, G. & Tam, J. P., eds.) Kluwer Academic Press, Dordrecht, The Netherlands, pp. 600–601 (2000).

[not indexed for MEDLINE]

88).
Sakmar, T. P.

Restoration of Compact Discs.

Nature Genet 25:245–246 (2000).

PMID: 10888860 [PubMed - indexed for MEDLINE]

87).
Lin, S. W., Han, M., & Sakmar, T. P.

Analysis of Functional Microdomains of Rhodopsin.

Methods Enzymol 315:116–130 (2000).

PMID: 10736698 [PubMed - indexed for MEDLINE]

86).
Fahmy, K., Sakmar, T. P., & Siebert, F.

Structural Determinants of Active Conformation of Rhodopsin: Molecular Biophysics Approaches.

Methods Enzymol 315:178–196(2000).

PMID: 10736702 [PubMed - indexed for MEDLINE]

85).
Han, M. & Sakmar, T. P.

Assays for the Activation of Recombinant Expressed Opsin by all-trans-Retinals.

Methods Enzymol 315:251–267 (2000).

PMID: 10736707 [PubMed - indexed for MEDLINE]

84).
Isele, J., ,Sakmar T. P. & Siebert, F.

Rhodopsin Activation Affects the Environment of Specific Neighboring Phospholipids: An FTIR Spectroscopic Study.

Biophys J 79:3063–3071 (2000).

PMID: 11106612 [PubMed - indexed for MEDLINE]

83).
Min, K. C., Gravina, S. A., & Sakmar, T. P.

Reconstitution of the Vertebrate Visual Cascade Using Recombinant Transducin Purified from Sf9 Cells.

Protein Expr Purification 20:514–526 (2000).

PMID: 11087692 [PubMed - indexed for MEDLINE]

82).
Fahmy, K., Sakmar, T. P. & Siebert, F.

Transducin-dependent Protonation of Glutamic Acid 134 in Rhodopsin.

Biochemistry 39:10607–10612 (2000).

PMID: 10956053 [PubMed - indexed for MEDLINE]

81).
Unson, C. G., Wu, C. –R., Sakmar, T. P.& Merrifield, R. B.

Selective Stabilization of the High-affinity Binding Conformation of Glucagon Receptor by the Long Splice Variant of Gas.

J Biol Chem 275:21631–21638 (2000).

PMID: 10791965 [PubMed - indexed for MEDLINE]

80).
Cormier, E. G., Persuh, M., Thompson, D. A. D., Lin, S. W., Sakmar, T. P., Olson, W. C. & Dragic, T.

Specific Interaction of CCR5 Amino-terminal Domain Peptides Containing Sulfo-Tyrosines with HIV-1 Envelope Glycoprotein gp120.

Proc Natl Acad Sci U S A 97:5762–5767 (2000).

PMID: 10823934 [PubMed - indexed for MEDLINE]

79).
Dragic, T., Trkola, A., Thompson, D. A. D., Cormier, E. G., Kajumo, F. A., Maxwell, E., Lin, S. W., Ying, W., Smith, S. O., Sakmar, T. P. & Moore, J. P.

A Binding Pocket for a Small Molecule Inhibitor of HIV-1 Entry Within the Transmembrane Helices of CCR5.

Proc Natl Acad Sci U S A 97:5639–5644 (2000).

PMID: 10779565 [PubMed - indexed for MEDLINE]

78).
Kazmi, M., Snyder, L. A., Cypess, A. M., Graber, S. G. & Sakmar, T. P.
Selective Reconstitution of Human D4 Dopamine Receptor Variants with Gia Subtypes.
Biochemistry 38:3734–3744 (2000).

PMID: 10736173 [PubMed - indexed for MEDLINE]

77).
Ernst, O. E., Meyer, C., Marin, E. P., Fu, W. –Y., Sakmar, T. P. & Hofmann, K. P.

Mutation of the Fourth Cytoplasmic Loop of Rhodopsin Affects Binding of Transducin and Peptides Derived from the Carboxyl-terminal Sequences of Transducin a and g Subunits.

J Biol Chem 275:1937–1943 (2000).

PMID: 10636895 [PubMed - indexed for MEDLINE]

76).
Marin, E. P., Gopala Krishna, A., Zyvaga, T. A., Isele, J., Siebert, F. & Sakmar, T. P.

The Amino-terminal Region of the Fourth Cytoplasmic Loop of Rhodopsin Modulates Rhodopsin-transducin Interaction.

J Biol Chem 275:1930–1936 (2000).

PMID: 10636894 [PubMed - indexed for MEDLINE]

75).
Lewis, J. W., Szundi, I., Fu, W. -Y., Sakmar, T. P. & Kliger, D. S.

pH Dependence of Photolysis Intermediates in the Photoactivation of Rhodopsin Mutant E113Q.

Biochemistry 39:599–606 (2000).

PMID: 10642185 [PubMed - indexed for MEDLINE]

74).
Sakmar, T. P.

Rhodopsin Early Receptor Potential Revisited.

Biophys J 77:1189–1190 (1999).

PMID: 10465733 [PubMed - indexed for MEDLINE]
PMCID: PMC1300410

73).
Lin, S. W. & Sakmar, T. P.

Colour Tuning Mechanism of Visual Pigments.

in Rhodopsins and Photo-transduction. Novartis Foundation Symposium No. 224. (Goode, J., ed.) John Wiley & Sons, Inc., New York, vol. 224, pp. 124–141 (1999).

PMID: 10614049 [PubMed - indexed for MEDLINE]

72).
Sakmar, T. P.

Rhodopsin.

in The Encyclopedia of Neuroscience. (Adelman, G. & Smith, B. H., eds.) Elsevier Science B.V., Amsterdam, Holland, pp. 1807–1810 (1999).

[not indexed for MEDLINE]

71).
Sakmar, T. P. & Min, K. C.

Lessons from Rhodopsin.

in Receptor Biochemistry and Methodology. Vol III - Structure/Function Analysis of GPCRs. (Wess, J., ed.) John Wiley & Sons, Inc., New York, vol. 3, pp. 85–107 (1999).

[not indexed for MEDLINE]

70).
cover70 Kochendoerfer, G. G., Lin, S. W., Sakmar, T. P. & Mathies, R. A.

How Color Visual Pigments Are Tuned.

Trends Biochem Sci 24:300–305 (1999).

PMID: 10431173 [PubMed - indexed for MEDLINE]

69).
Simpson, M. M., Ballesteros, J. A., Chiappa, V., Chen, J., Suehiro, M., Hartman, D. S., Godel, T., Snyder, L. A., Sakmar, T. P. & Javitch, J. A.

Dopamine D4/D2 Receptor Selectivity Is Determined by a Divergent Aromatic Microdomain Contained within the Second, Third, and Seventh Membrane-Spanning Segments.

Mol Pharmacol 56:1116–1126 (1999).

PMID: 10570038 [PubMed - indexed for MEDLINE]

68).
Cypess, A. M., Unson, C. G., Wu, C. –R. & Sakmar, T. P.

Two Cytoplasmic Loops of the Glucagon Receptor Are Required to Elevate cAMP or Intracellular Calcium.

J Biol Chem 274:19455–19464 (1999).

PMID: 10383462 [PubMed - indexed for MEDLINE]

67).
Sakmar, T. P.

Rhodopsin: a Prototypical G Protein-coupled Receptor.

Progr Nucleic Acid Res Mol Biol 59:1–34 (1998).

PMID: 9427838 [PubMed - indexed for MEDLINE]

66).
Beck, M., Siebert, F. & Sakmar, T. P.

Evidence for the Specific Interaction of a Lipid Molecule with Rhodopsin Which Is Altered in the Transition to the Active State Metarhodopsin II.

FEBS Lett 436:304–308 (1998).

PMID: 9801137 [PubMed - indexed for MEDLINE]

65).
Lin, S. W., Kochendoerfer, G. G., Carroll, K. S., Wang, D., Mathies, R. A. & Sakmar, T. P.

Mechanisms of Spectral Tuning in Blue Cone Visual Pigments. Visible and Raman Spectroscopy of Blue-Shifted Rhodopsin Mutants.

J Biol Chem 273:24583–24591 (1998).

PMID: 9733753 [PubMed - indexed for MEDLINE]

64).
Beck, M., Sakmar, T. P. & Siebert, F.

Spectroscopic Evidence for Interaction Between Transmembrane Helices 3 and 5 in Rhodopsin.

Biochemistry 37:7630–7639 (1998).

PMID: 9585578 [PubMed - indexed for MEDLINE]

63).
Han, M., Smith, S. O. & Sakmar, T. P.

Constitutive Activation of Opsin by Mutation of Methionine 257 on Transmembrane Helix 6.

Biochemistry 37:8253–8261 (1998).

PMID: 9609722 [PubMed - indexed for MEDLINE]

62).
Dragic, T., Trkola, A., Lin, S. W., Nagashima, K., Kajumo, F., Allaway, G., Wu, L., MacKay, C., Sakmar, T. P., Maddon, P. J. & Moore, J. P.

N-Terminal Substitutions in the CCR5 Co-receptor Impair gp120 Binding and HIV-1 Entry.

J Virol 72:279–284 (1998).

PMID: 9420225 [PubMed - indexed for MEDLINE]

61).
Han, M., Groesbeek, M., Smith, S. O. & Sakmar, T. P.

The Role of the C9-Methyl Group in Rhodopsin Activation: Characterization of Mutant Opsins with the Artificial Chromophore 11-cis-9-demethyl-Retinal.

Biochemistry 37:538–545 (1998).
PMID: 9425074 [PubMed - indexed for MEDLINE]

60).
Donzella, G. A., Schols, D., Lin, S. W., Esté, J. A., Nagashima, K. A., Maddon, P. J., Allaway, G. P., Sakmar, T. P., Henson, G., De Clercq, E. & Moore, J. P.

AMD3100, a Small Molecule Inhibitor of HIV-1 Entry via the CXCR4 Co-receptor.

Nature Med 4:72–77 (1998).

PMID: 9427609 [PubMed - indexed for MEDLINE]

59).
Sakmar, T. P.

Chemistry of Vision.

in Macmillan Encyclopedia of Chemistry . (Lagowski, J. J., ed.) Macmillan Reference USA, New York, vol. 4, pp. 1492–1495 (1997).

[not indexed for MEDLINE]

58).
Sakmar, T. P.

Rhodopsin.

in The Encyclopedia of Neuroscience . (Adelman, G. & Smith, B. H., eds.) Elsevier Science B.V., Amsterdam, Holland, CD-ROM (1997).

[not indexed for MEDLINE]

57).
Han, M., Groesbeek, M., Sakmar, T. P. & Smith, S. O.

The C9-Methyl Group of Retinal Interacts with Glycine 121 in Rhodopsin.

Proc Natl Acad Sci U S A 94:13442–13447 (1997).

PMID: 9391044 [PubMed - indexed for MEDLINE]

56).
Jäger, S., Han, M., Lewis, J. W., Szundi, I., Sakmar, T. P. & Kliger, D. S.

Properties of Early Photolysis Intermediates of Rhodopsin Are Regulated by Glycine 121 and Phenylalanine 261.

Biochemistry 36:11804–11810 (1997).

PMID: 9305971 [PubMed - indexed for MEDLINE]

55).
Han, M., Lou, J., Nakanishi, K., Sakmar, T. P. & Smith, S. O.

Partial Agonist Activity of 11-cis-Retinal in Rhodopsin Mutants.

J Biol Chem 272:23081–23085 (1997).

PMID: 9287308 [PubMed - indexed for MEDLINE]

54).
Jäger, S., Lewis, J. W., Zyvaga, T. A., Szundi, I., Sakmar, T. P. & Kliger, D. S.

Chromophore Structural Changes in Rhodopsin From Nanoseconds to Microseconds Following Pigment Photolysis.

Proc Natl Acad Sci U S A 94:8557–8562 (1997).

PMID: 9238015 [PubMed - indexed for MEDLINE]

Sheih, T., Han, M., Sakmar, T. P. & Smith, S. O.

The Steric Trigger in Rhodopsin Activation.

J Mol Biol 269:373–384 (1997).

PMID: 9199406 [PubMed - indexed for MEDLINE]

52).
Jäger, S., Lewis, J. W., Zyvaga, T. A., Szundi, I., Sakmar, T. P. & Kliger, D. S.

Time-resolved Spectroscopy of the Early Photolysis Intermediates of Rhodopsin Schiff Base Counterion Mutants.

Biochemistry 36:1999–2009 (1997).

PMID: 9047297 [PubMed - indexed for MEDLINE]

51).
Kazmi, M. A., Sakmar, T. P. & Ostrer, H.

Mutation of a Conserved Cysteine in the X-linked Cone Opsins Disrupts Targeting and Causes Color Vision Deficiencies.

Invest Ophthalmol Vis Sci 38:1074–1081 (1997). [*Cover Article]

PMID: 9152227 [PubMed - indexed for MEDLINE]

50).
Sakmar, T. P.

Molecular Mechanism of Signal Transduction by Rhodopsin.

in G Protein-coupled Receptors : New Opportunities for Commercial Development . (Mulford, N., ed.) I.B.C., Inc., Southborough, MA, pp. 638–665 (1996).

49).
Fahmy, K., Zyvaga, T. A., Sakmar, T. P. & Siebert, F.

Spectroscopic Evidence for Altered Chromophore-Protein Interactions in Low Temperature Photoproducts of the Visual Pigment Responsible for Congenital Night Blindness.

Biochemistry 35:15065–15073 (1996).

MID: 8942673 [PubMed - indexed for MEDLINE]

48).
Han, M., Lin, S. W., Minkova, M., Smith, S. O. & Sakmar, T. P.

Functional Interaction of Transmembrane Helices 3 and 6 in Rhodopsin. Replacement of Phenylalanine 261 by Alanine Causes Reversion of Phenotypes of Glycine 121 Replacement Mutants.

J Biol Chem 271:32337–32342 (1996).

PMID: 8943296 [PubMed - indexed for MEDLINE]

47).
Han, M., Lin, S. W., Smith, S. O. & Sakmar, T. P.

The Effects of Amino Acid Replacements of Glycine 121 on Transmembrane Helix 3 of Rhodopsin.

J Biol Chem 271:32330–32336 (1996).

PMID: 8943295 [PubMed - indexed for MEDLINE]

46).
Sheikh, S., Zyvaga, T. A., Lichtarge, O., Sakmar, T. P. & Bourne, H. R.

Rhodopsin Activation Blocked by Metal-Ion-Binding Sites Linking Transmembrane Helices C and F.

Nature 383:347–350 (1996).

PMID: 8848049 [PubMed - indexed for MEDLINE]

45).
Lin, S. W. & Sakmar, T. P.

Specific Tryptophan UV-Absorbance Changes Are Probes of the Transition of Rhodopsin to Its Active State.

Biochemistry 35:11149–11159 (1996).

PMID: 8780519 [PubMed - indexed for MEDLINE]

44).
Zyvaga, T. A., Fahmy, K., Siebert, F. & Sakmar, T. P.

Characterization of the Mutant Visual Pigment Responsible for Congenital Night Blindness: a Biochemical and Fourier-Transform Infrared Spectroscopy Study.

Biochemistry 35:7536–7545 (1996).

PMID: 8652533 [PubMed - indexed for MEDLINE]

43).
Unson, C. G., Cypess, A. M., Wu, C. -R., Goldsmith, P. K., Merrifield, R. B. & Sakmar, T. P.

Antibodies Against Specific Extracellular Epitopes of the Glucagon Receptor Block Glucagon Binding.

Proc Natl Acad Sci U S A 93:310–315 (1996).

PMID: 8552628 [PubMed - indexed for MEDLINE]

42).
Sakmar, T. P. & Fahmy, K.

Properties and Photoactivity of Rhodopsin Mutants.

Israel J Chem 35:325–338 (1995).

[not indexed for MEDLINE]

41).
Beck, M., Sakmar, T. P. & Siebert, F.

FTIR Investigations of Rhodopsin and Rhodopsin Mutants in Detergent and Reconstituted into Membranes.

in Sixth European Conference on the Spectroscopy of Biological Molecules (Merlin, J. C., Turrell, S. & Huvenne, J. P., eds.) Kluwer Academic Publishers, Dordrecht, Netherlands, pp. 173–174 (1995).

[not indexed for MEDLINE]

40).
Fahmy, K., Siebert, F. & Sakmar, T. P.

Molecular Determinants of the Active Conformation of Rhodopsin Studied by Attenuated Total Reflectance FTIR Difference Spectroscopy.

in Sixth European Conference on the Spectroscopy of Biological Molecules (Merlin, J. C., Turrell, S. & Huvenne, J. P., eds.) Kluwer Academic Publishers, Dordrecht, Netherlands, pp. 171–172 (1995).

[not indexed for MEDLINE]

39).
Unson, C. G., Cypess, A. M., Kim, H. N., Carruthers, C. J. L., Goldsmith, P. K., Merrifield, R. B. & Sakmar, T. P.

Characterization of Deletion and Truncation Mutants of the Rat Glucagon Receptor: Seven Transmembrane Segments Are Necessary for Receptor Transport to the Plasma Membrane and Glucagon Binding.

J Biol Chem 270:27720–27727 (1995).

PMID: 7499239 [PubMed - indexed for MEDLINE]

38).
Garcia, P. D., Onrust, R., Bell, S. M., Sakmar, T. P. & Bourne, H. R.

Transducin-a Carboxyl-Terminal Mutations Prevent Activation by Rhodopsin: A New Assay Using Recombinant Proteins Expressed in Cultured Cells.

EMBO J 14:4460–4469 (1995).

PMID: 7556089 [PubMed - indexed for MEDLINE]

37).
Fahmy, K., Siebert, F. & Sakmar, T. P.

The Photoactivated State of Rhodopsin and How It Can Form.

Biophys Chem 56:171–181 (1995).

PMID: 7662864 [PubMed - indexed for MEDLINE]

36).
Ernst, O., Hofmann, K. P. & Sakmar, T. P.

Characterization of Rhodopsin Mutants That Bind Transducin But Fail To Induce GTP Nucleotide Uptake: Classification of Mutant Pigments by Fluorescence, Nucleotide Uptake, and Light-Scattering Assays.

J Biol Chem 270:10580–10586 (1995).

PMID: 7737995 [PubMed - indexed for MEDLINE]

35).
Carruthers, C. J. L. & Sakmar, T. P.

Synthesis and Expression of Synthetic Genes: Applications to Structure-Function Studies of Receptors.

Methods Neurosci 25:322–344 (1995).

[not indexed for MEDLINE]

34).
Sakmar, T. P.

Opsins.

in Handbook of Receptors and Channels (Vol. I: G Protein-coupled Receptors) (Peroutka, S. J., ed.) CRC Press, Boca Raton, v. I, pp. 257–276 (1994).

[not indexed for MEDLINE]

33).
Fahmy, K., Siebert, F. & Sakmar, T. P.

A Mutant Rhodopsin Photoproduct with a Protonated Schiff Base Displays an Active-state Conformation: a Fourier-Transform Infrared Spectroscopy Study.

Biochemistry 33:13700–13705 (1994).

PMID: 7947779 [PubMed - indexed for MEDLINE]

32).
Carruthers, C. J. L., Unson, C. G., Kim, H. N. & Sakmar, T. P.

Synthesis and Expression of a Gene for the Rat Glucagon Receptor. Replacement of an Aspartic Acid in the Extracellular Domain Prevents Glucagon Binding.

J Biol Chem 269:29321–29328 (1994).

PMID: 7961903 [PubMed - indexed for MEDLINE]

31).
Jäger, F., Fahmy, K., Sakmar, T. P. & Siebert, F.

Identification of Glutamic Acid 113 as the Schiff Base Proton Acceptor in the Metarhodopsin II Photointermediate of Rhodopsin.

Biochemistry 33:10878–10882 (1994).

PMID: 7916209 [PubMed - indexed for MEDLINE]

30).
Arnis, S., Fahmy, K., Hofmann, K. P. & Sakmar, T. P.

A Conserved Carboxylic Acid Group Mediates Light-Dependent Proton Uptake and Signaling by Rhodopsin.

J Biol Chem 269:23879–23881 (1994).

PMID: 7929034 [PubMed - indexed for MEDLINE]

29).
Zyvaga, T. A., Fahmy, K. & Sakmar, T. P.

Characterization of Rhodopsin-Transducin Interaction: A Mutant Rhodopsin Photoproduct with a Protonated Schiff Base Activates Transducin.
Biochemistry 33:9753-9761 (1994).

PMID: 8068654 [PubMed - indexed for MEDLINE]

28).

Jäger, F., Sakmar, T. P. & Siebert, F.

Molecular Changes of the Membrane-Embedded Carboxyl Group Glu-122 of Bovine Rhodopsin During the Transition to the Active State Metarhodopsin II: An Investigation of the Glu-122 to Asp Mutant Using FT-IR Difference Spectroscopy.

in Fifth International Conference on the Spectroscopy of Biological Molecules (Theophanides, T., Anatassopoulou, J. & Fotopoulos, N., eds.) Kluwer Academic Publishers, Dordrecht, Netherlands, pp. 223-226 (1993).

[not indexed for MEDLINE]

27).
Fahmy, K., Jäger, F., Beck, M., Zyvaga, T. A., Sakmar, T. P. & Siebert, F.

Protonation States of Membrane-Embedded Carboxylic Acid Groups in Rhodopsin and Metarhodopsin II: A Fourier-Transform Infrared Spectroscopy Study of Site-Directed Mutants.

Proc Natl Acad Sci U S A 90:10206–10210 (1993).

PMID: 7901852 [PubMed - indexed for MEDLINE]

26).
Fahmy, K. & Sakmar, T. P.

Light-Dependent Transducin Activation by an Ultraviolet-Absorbing Rhodopsin Mutant.

Biochemistry 32:9165–9171 (1993).

PMID: 8396426 [PubMed - indexed for MEDLINE]

25).
Fahmy, K. & Sakmar, T. P.

Regulation of the Rhodopsin-Transducin Interaction by a Highly Conserved Carboxylic Acid Group.

Biochemistry 32:7229–7236 (1993).

PMID: 8343512 [PubMed - indexed for MEDLINE]

24).
Min, K. C., Zyvaga, T. A., Cypess, A. M. & Sakmar, T. P.

Characterization of Mutant Rhodopsins Responsible for Autosomal Dominant Retinitis Pigmentosa. Mutations on the Cytoplasmic Surface Affect Transducin Activation.

J Biol Chem 268:9400–9404 (1993).

PMID: 8486634 [PubMed - indexed for MEDLINE]

23).
Zyvaga, T. A., Min, K. C., Beck, M. & Sakmar, T. P.

Movement of the Retinylidene Schiff Base Counterion in Rhodopsin by One Helix Turn Reverses the pH Dependency of the Metarhodopsin I to Metarhodopsin II Transition.

J Biol Chem 268:4661–4667 (1993). Correction: J Biol Chem 269:13056 (1994).

PMID: 8444840 [PubMed - indexed for MEDLINE]

22).
Sakmar, T. P., Fahmy, K., Chan, T. & Lee, M.

Mutagenesis Studies of Rhodopsin Phototransduction.

in Structures and Functions of Retinal Proteins (Rigaud, J. L., ed.) Libbey, London, pp. 67-70 (1992).

[not indexed for MEDLINE]

21).

Sakmar, T. P.
The Traveler's Medical Kit.

Infect Dis Clin North Am 6:355–370 (1992).

PMID: 1624781 [PubMed - indexed for MEDLINE]

20).
Chan, T., Lee, M. & Sakmar, T. P.

Introduction of Hydroxyl-Bearing Amino Acids Causes Bathochromic Spectral Shifts in Rhodopsin: Amino Acid Substitutions Responsible for Red-Green Color Pigment Spectral Tuning.

J Biol Chem 267:9478–9480 (1992).

PMID: 1577792 [PubMed - indexed for MEDLINE]

19).
Sakmar, T. P., Franke, R. R. & Khorana, H. G.

Mutagenesis Studies of Rhodopsin Phototransduction.

in Signal Transduction in Photoreceptor Cells (Hargrave, P. A., Hofmann, K. P. & Kaupp, U. B., eds.) Springer-Verlag, Berlin, pp. 21–30 (1992).

[not indexed for MEDLINE]

18).
Lin, S. W., Sakmar, T. P., Franke, R. R., Khorana, H. G. & Mathies, R. A.

Resonance Raman Microprobe Spectroscopy of Rhodopsin Mutants: Effects of Substitutions in the Third Transmembrane Helix.

Biochemistry 31:5105–5111 (1992).

[not indexed for MEDLINE]

17).
Franke, R. R., Sakmar, T. P., Graham, R. M. & Khorana, H. G.
Structure and Function in Rhodopsin. Studies of the Interaction Between the Rhodopsin Cytoplasmic Domain and Transducin.
J Biol Chem 267:14767–14774 (1992).

PMID: 1634520 [PubMed - indexed for MEDLINE]

16).
Sakmar, T. P., Franke, R. R. & Khorana, H. G.

The Role of the Retinylidene Schiff Base Counterion in Rhodopsin in Determining Wavelength Absorbance and Schiff Base pKa.

Proc Natl Acad Sci U S A 88:3079–3083 (1991).

[not indexed for MEDLINE]

15).
Franke, R. R., König, B., Sakmar, T. P., Khorana, H. G. & Hofmann, K. P.

Rhodopsin Mutants That Bind But Fail to Activate Transducin.

Science 250:123–125 (1990).

PMID: 2218504 [PubMed - indexed for MEDLINE]

14).
Sakmar, T. P., Franke, R. R. & Khorana, H. G.

Glutamic Acid 113 Serves as the Retinylidene Schiff Base Counterion in Bovine Rhodopsin.

Proc Natl Acad Sci U S A 86:8309–8313 (1989).

PMID: 2573063 [PubMed - indexed for MEDLINE]
PMCID: PMC298270

13).
Karnik, S. S., Sakmar, T. P., Chen, H. -B. & Khorana, H. G.

Cysteine Residues 110 and 187 are Required for the Formation of Correct Structure in Bovine Rhodopsin.

Proc Natl Acad Sci U S A 85:8459–8463 (1988).

MID: 3186735 [PubMed - indexed for MEDLINE]
PMCID: PMC282477

12).
Sakmar, T. P. & Khorana, H. G.

Total Synthesis and Expression of a Gene for the a-Subunit of Bovine Rod Outer Segment Guanine Nucleotide-Binding Protein (Transducin).

Nucleic Acids Res 16:6361–6372 (1988).

[not indexed for MEDLINE]

11).
Franke, R. R., Sakmar, T. P., Oprian, D. D. & Khorana, H. G.

A Single Amino Acid Substitution in Rhodopsin ( Lysine 248 –-> Leucine) Prevents Activation of Transducin.

J Biol Chem 263:2119–2122 (1988).

PMID: 3123487 [PubMed - indexed for MEDLINE]

10).
Braiman, M., Bubis, J., Doi, T., Chen, H. -B., Flitsch, S. L., Franke, R. R., Gilles-Gonzalez, M. A., Graham, R. M., Karnik, S. S., Khorana, H. G., Knox, B. E., Krebs, M. P., Marti, T., Mogi, T., Nakayama, T., Oprian, D. D., Puckett, K. L., Sakmar, T. P., Stern, L. J., Subramaniam, S. & Thompson, D. A.

Studies on Light Transduction by Bacteriorhodopsin and Rhodopsin.

Cold Spring Harbor Symp Quant Biol 53:355–364 (1988).

[not indexed for MEDLINE]

9).
Franke, R. R., Sakmar, T. P., Graham, R. M. & Khorana, H. G.

Structure-Function Studies of Bovine Rhodopsin: Interactions with Transducin.

in Molecular Biology of the Eye: Genes, Vision and Ocular Disease(Piatigorsky, J., Zelenka, P. & Shinohara, T., eds.), Alan R. Liss, Inc., New York, pp. 45–52 (1988).

[not indexed for MEDLINE]

8).
Karnik, S. S., Sakmar, T. P., Franke, R. R., Knox, B. E., Oprian, D. D., Chen, H. -B. & Khorana, H. G.

Site-Specific Mutagenesis of Bovine Rhodopsin.

in Molecular Biology of the Eye: Genes, Vision and Ocular Disease (Piatigorsky, J., Zelenka, P., & Shinohara, T., eds.), Alan R. Liss, Inc., New York, pp. 23–34 (1988).

[not indexed for MEDLINE]

7).
Oprian, D., Sakmar, T. P., Nakayama, T., Chen, H. -B., Knox, B., Karnik, S., Franke, R. & Khorana, H. G.

Molecular Biological Studies of the Visual Pigment, Rhodopsin.

Discuss Neurosci 4:20–28 (1987).

[not indexed for MEDLINE]

6).
Ackerman, R. H., Richardson, E. P., Davis, K. R., Boom, W. H., Sakmar, T. P. & Haley, E. C.

Abrupt Onset of Headache Followed by Rapidly Progressive Encephalopathy in a 30-Year Old Woman - Angiitis of Central Nervous System (CPC).

N Engl J Med 313:566–575 (1985).

[not indexed for MEDLINE]

5).
Seid, R. C., Jr. & Sakmar, T. P.

A Differential Labeling Model for Determining the Number of Catalytically Essential Carboxyl Groups in Fumarase.

Biochim Biophys Acta (BBA) Enzymology 662:196–201 (1981).

[not indexed for MEDLINE]

4).
Randolph, A., Sakmar, T. P. & Heinrikson, R. L.

Phospholipases A2 - Structure, Function, and Evolution.

in Frontiers in Protein Chemistry (Liu, T. -Y. & Yasunobu, K., eds.) Elsevier, Amsterdam, pp. 297–322 (1980).

[not indexed for MEDLINE]

3).
Liang, S. M., Sakmar, T. P. & Liu, T. -Y.

Purification of an Endotoxin-Binding Protein from Limulus Amoebocyte Membranes.

J Biol Chem 255:5586–5590 (1980).

[not indexed for MEDLINE]

2).
Liu, T. -Y., Seid, R. C., Tai, J. Y., Liang, S. -M., Sakmar, T. P. & Robbins, J. B.

Studies on Limulus Lysate Coagulating System.

in Biomedical Applications of the Horseshoe Crab (Limulidae) (Cohen, E. B., ed.) Alan R. Liss, Inc., New York, pp. 147–158 (1979).

[not indexed for MEDLINE]

1).
Liu, T. -Y., Seid, R. C., Tai, J. Y., Liang, S. -M., Sakmar, T. P. & Robbins, J. B.

Studies on Limulus Lysate Coagulating System.

Prog Clin Biol Res 29:147–158 (1979).

[not indexed for MEDLINE]

3).
Sakmar, T. P., Gardner, P. & Peterson, G. N.

Health Guide for International Travelers. 2nd edition.

Passport Books, National Textbook Co., Lincolnwood, IL. 171 pp. (1994).

2).
book2cover
Sakmar, T. P., Gardner, P. & Peterson, G. N.

Health Guide for International Travelers.

Passport Books, National Textbook Co., Lincolnwood, IL. 143 pp. (1991 reprint).

1).
book1cover Sakmar, T. P., Gardner, P. & Peterson, G. N.

Health Guide for International Travelers.

Passport Books, National Textbook Co., Lincolnwood, IL. 143 pp. (1989).