Joel Sussman Explained
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
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
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 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;
- 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
External links
Notes and References
- 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.
- 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.
- 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
- 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.
- 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
- 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
- https://fold.proteopedia.org/cgi-bin/findex
- 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.
- 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.
- 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
- 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
- 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
