|Born||24 September 1943|
|Institutions||Weizmann Institute of Science|
|Known for||Studies on acetylcholinesterase|
Samuel and Paula Elkeles Prize (2005)|
Teva Founders' Award (2006)
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. Born in Philadelphia, he is the Morton and Gladys Pickman Professor of Structural Biology at the Weizmann Institute of Science in Rehovot and the director of the Israel Structural Proteomics Center there.
Formal education and training
In 1965, Sussman got his B.A. at the Cornell University in math and physics. He got his PhD from MIT in biophysics in 1972 with Cyrus Levinthal. Sussman later did 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
Sussman held the following positions at the Weizmann Institute of Science:
- 1976–80 – Senior Scientist
- 1980–92 – Associate Professor
- 1992–date – Professor
- 1984–85 – Head, Department of Structural Chemistry
- 1988–89 – Head, Kimmelman Center for Biomolecular Structure and Assembly
- 2002–date – Incumbent of the Morton and Gladys Pickman Chair of Structural Biology
In 1994–99, he was also the director of the Protein Data Bank (PDB) at the Brookhaven National Laboratory.
Scientific interests and contributions
Sussman was a pioneer of macromolecular refinement, developing CORELS and applying it to yeast tRNAphe. He subsequently determined the structures of 'bulge'-containing DNA fragments as models for insertion mutations.
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;
- π-cation interactions play a key role in binding of acetylcholine (ACh) and ligands to AChE;
- Its ACh-binding site assisted in structure-based design of promising leads for novel anti-Alzheimer's drugs;
- Discovered a highly asymmetric charge distribution conserved in 'cholinesterase-like adhesion molecules' (CLAMs), and showed that their cytoplasmic domains are 'intrinsically unfolded' with implications for neural development and plasticity, and led to an algorithm, for predicting whether a protein sequence will fold;
- A novel anchoring device for AChE involving superhelical assembly of its subunits around a polyproline-II helix;
- The specific chemical and structural damage to proteins produced by synchrotron radiation, e.g. cleavage of a specific disulfide bond even at cryo temperatures.
He has investigated the molecular basis for halophilicity and halotolerance, shedding light on the molecular basis of how proteins function over extreme ranges of salt concentration, with unexpected implications for kidney diseases. Recently, he determined the structures of acid-β-glucosidase, a protein defective in Gaucher disease, paving the way to novel therapeutic approaches, and of paraoxonase, a protein relevant to treatment of atherosclerosis.
Honors and awards
- 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)
- J.L Sussman & S.-H. Kim (1976) "Three-dimensional structure of a transfer RNA in two crystal forms" Science 192, 853-858 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, 800-804 Abstract
- 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
- 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
- H. Dvir, M. Harel, S. Bon, W.-Q. Liu, M. Vidal, C. Garbay, J.L. Sussman, J. Massoulié & I. Silman (2004) "The synaptic acetylcholinesterase tetramer assembles around a polyproline-II helix" EMBO J. 23, 4394-4405 doi:10.1038/sj.emboj.7600425 PMID 15526038
- 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
- O. Dym, M. Mevarech & J.L. Sussman (1995) "Structural features that stabilize Halophilic malate dehydrogenase from an Archaebacterium" Science 267, 1344-1346 Abstract
- 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