Joel Sussman Explained

Joel Sussman
Birth Date:	24 September 1943
Nationality:	Israeli
Field:	Crystallography
Work Institution:	Weizmann Institute of Science
Alma Mater:	Cornell University MIT Hebrew University
Known For:	Studies on acetylcholinesterase
Prizes:	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. He is Professor Emeritus of Structural Biology at the Weizmann Institute of Science in Rehovot and is Co-Director of the Israel Structural Proteomics Center.

Early life and education

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, under Cyrus Levinthal. He postdocted at the Hebrew University of Jerusalem in 1972, with Yehuda Lapidot, and at Duke University in 1973-76 with Sung-Hou Kim.

Appointments and positions held

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

Sussman was a pioneer of macromolecular refinement, developing CORELS and applying it to yeast tRNA^phe.^{[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;
• Its ACh-binding site assisted in structure-based design of promising leads for novel anti-Alzheimer's drugs;
• Discovered that the cytoplasmic portion of 'cholinesterase-like adhesion molecules' (CLAMs) are 'intrinsically disordered'^[5] that led to an algorithm, FoldIndex,^[6] 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.^[7]

He has investigated the molecular basis as to how proteins function under extreme conditions ^{[8] [9]} with unexpected implications for kidney diseases. He determined the structures of Glucocerebrosidase,^[10] a protein defective in Gaucher disease, paving the way to novel therapeutic approaches, and of paraoxonase,^[11] 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)

External links

• Joel Sussman at the Weizmann Institute
• The Israel Structural Proteomics Center

Notes and References

1. J.L. Sussman . S.-H. Kim . 1976. Three-dimensional structure of a transfer RNA in two crystal forms. Science. 192. 4242 . 853–858 . 10.1126/science.775636 . 775636.
2. 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 . 10.1107/S0567739477001958.
3. 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
4. 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.
5. 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
6. Web site: FoldIndex . fold.proteopedia.org.
7. 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.
8. O.. Dym. M.. Mevarech . J.L.. Sussman . 1995. Structural features that stabilize Halophilic malate dehydrogenase from an Archaebacterium. Science. 267. 5202. 1344–1346 . 10.1126/science.267.5202.1344. 17812611. 20750377.
9. 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
10. 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
11. 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