Joel Sussman
 | This article may be too technical for most readers to understand. (August 2012) |
Joel Sussman | |
|---|---|
| Born | 24 September 1943 |
| Nationality | Israeli |
| Alma mater | Cornell University MIT Hebrew University |
| Known for | Studies on acetylcholinesterase |
| Awards | Samuel and Paula Elkeles Prize (2005) Teva Founders' Award (2006) |
| Scientific career | |
| Fields | Crystallography |
| Institutions | Weizmann Institute of Science |
Joel L. Sussman (born September 24, 1943) is an Israeli crystallographer best known for his studies on acetylcholinesterase, a key protein involved in transmission of nerve signals. He is the Morton and Gladys Pickman Professor of Structural Biology at the Weizmann Institute of Science in Rehovot and its director of the Israel Structural Proteomics Center.
Early life and education
[edit]Sussman was born in Philadelphia, Pennsylvania.
In 1965, Sussman received his B.A. at Cornell University in math and physics. He received his PhD from MIT in biophysics in 1972, having worked with Cyrus Levinthal. Sussman conducted postdoctoral research in the Hebrew University of Jerusalem in 1972, with Yehuda Lapidot, and in the Duke University in 1973 with Sung-Hou Kim.
Appointments and positions held
[edit]Sussman has been a Professor at the Weizmann Institute of Science since 1976.
- 1984–85 – Head, Department of Structural Chemistry
- 1988–89 – Head, Kimmelman Center for Biomolecular Structure and Assembly
- 2002–14 – Incumbent of the Morton and Gladys Pickman Chair of Structural Biology
- 2016-now – Professor Emeritus
In 1994–99, he was also the director of the Protein Data Bank (PDB) at the Brookhaven National Laboratory.
Scientific interests and contributions
[edit]Sussman was a pioneer of macromolecular refinement, developing CORELS and applying it to yeast tRNAphe.[1][2] He subsequently determined the structures of 'bulge'-containing DNA fragments as models for insertion mutations.[3]
Sussman's current research focuses on nervous system proteins, especially acetylcholinesterase (AChE), whose 3D structure was first determined in his lab. This structure revealed:
- AChE is a prototype of the α/β hydrolase fold;[4]
- π-cation interactions play a key role in binding of acetylcholine (ACh) and ligands to AChE;[4]
- Its ACh-binding site assisted in structure-based design of promising leads for novel anti-Alzheimer's drugs;
- Discovered a highly asymmetric charge distribution[5] conserved in 'cholinesterase-like adhesion molecules' (CLAMs), and showed that their cytoplasmic domains are 'intrinsically disordered'[6] with implications for neural development and plasticity, and led to an algorithm, FoldIndex,[7] for predicting whether a protein sequence will fold;
- The specific chemical and structural damage to proteins produced by synchrotron radiation, e.g. cleavage of a specific disulfide bond even at cryo temperatures.[8]
He has investigated the molecular basis for halophilicity[9] and halotolerance,[10] shedding light on how proteins function over extreme ranges of salt concentration, with unexpected implications for kidney diseases. He determined the structures of Glucocerebrosidase,[11] a protein defective in Gaucher disease, paving the way to novel therapeutic approaches, and of paraoxonase,[12] a protein relevant to treatment of atherosclerosis.
Honors and awards
[edit]- 2014 - Ilanit-Katzir Prize for exceptional achievements in the field of Life Sciences (together with Israel Silman)
- 2006 – Teva Founders' Award for breakthroughs in molecular medicine (together with Hermona Soreq and Israel Silman).
- 2005 – Honorary Professor, Chinese Academy of Sciences
- 2005 – Samuel and Paula Elkeles Prize for Outstanding Scientist in the field of medicine in Israel (together with Israel Silman)
- 1994 – Elected member, European Molecular Biology Organization (EMBO)
References
[edit]- ^ J.L. Sussman; S.-H. Kim (1976). "Three-dimensional structure of a transfer RNA in two crystal forms". Science. 192 (4242): 853–858. doi:10.1126/science.775636. PMID 775636.
- ^ J.L. Sussman; S.R. Holbrook; G.M. Church; S.-H. Kim (1977). "A structure-factor least squares refinement procedure for macromolecular structures using constrained and restrained parameters". Acta Crystallogr. A33 (5): 800–804. doi:10.1107/S0567739477001958.
- ^ L. Joshua-Tor, D. Rabinovich, H. Hope, F. Frolow, E. Appella & J.L. Sussman (1988) "The three-dimensional structure of a DNA duplex containing looped out bases" Nature 334, 82-84 PMID 3386751
- ^ a b J.L. Sussman, M. Harel, F. Frolow, C. Oefner, A. Goldman, L. Toker & I. Silman (1991) "Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein" Science 253, 872-879. PMID 1678899
- ^ D.R. Ripoll, C.H. Faerman, P. Axelsen, I. Silman & J.L. Sussman (1993) "An electrostatic mechanism for substrate guidance down the aromatic gorge of acetylcholinesterase" Proc. Natl. Acad. Sci. USA 90, 5128-5132 PMID 8506359
- ^ T. Zeev-Ben-Mordehai, E.H. Rydberg, A. Solomon, L. Toker, S. Botti, V.J. Auld, I. Silman & J.L. Sussman (2003) "The intracellular domain of the drosophila cholinesterase-like neural adhesion protein, gliotactin, is natively unfolded" Proteins 53, 758-767 PMID 14579366
- ^ https://fold.proteopedia.org/cgi-bin/findex [bare URL]
- ^ Weik, M., Ravelli, R.B.G., Kryger, G., McSweeney, S., Raves, M., Harel, M., Gros, P., Silman, I., Kroon, J. & Sussman, J.L. (2000) "Specific chemical and structural damage to proteins produced by synchrotron radiation" Proc. Natl. Acad. Sci. USA 97, 623-628. PMID 10639129
- ^ Dym, O.; Mevarech, M.; Sussman, J.L. (1995). "Structural features that stabilize Halophilic malate dehydrogenase from an Archaebacterium". Science. 267 (5202): 1344–1346. doi:10.1126/science.267.5202.1344. PMID 17812611. S2CID 20750377.
- ^ L. Premkumar, H.M. Greenblatt, U. Bagashwar, T. Savchenkoa, I. Gokhmana, J.L. Sussman & A. Zamir (2005) "3D structure of a halotolerant algal carbonic anhydrase predicts halotolerance of a mammalian homolog" Proc. Natl. Acad. Sci. USA 102, 7493-7498 PMID 15894606
- ^ H. Dvir, M. Harel, A.H. McCarthy, L. Toker, I. Silman, A.H. Futerman & J.L. Sussman. X-ray structure of human acid-β-glucosidase, the defective enzyme in Gaucher disease (2003) EMBO Rep. 4, 704-709 PMID 12792654
- ^ M. Harel, A. Aharoni, L. Gaidukov, B. Brumshtein, O. Khersonsky, S. Yagur, R. Meged, H. Dvir, R.B.G. Ravelli, A. McCarthy, L. Toker, I. Silman, J.L. Sussman & D.S. Tawfik (2004) "3D-Structure, mechanism and evolution of serum paraoxonases – a family of detoxifying and anti-atherosclerotic enzymes" Nat. Struct. Mol. Biol. 11, 412-419 PMID 15098021
External links
[edit]- Joel Sussman at the Weizmann Institute
- The Israel Structural Proteomics Center