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.
Sussman was a pioneer of macromolecular refinement, developing CORELS and applying it to yeasttRNAphe.[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:
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)
^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. PMID775636.
^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" Nature334, 82-84 PMID3386751
^ abJ.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" Science253, 872-879. PMID1678899
^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" Proteins53, 758-767 PMID14579366
^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. USA97, 623-628. PMID10639129
^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. USA102, 7493-7498 PMID15894606
^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 PMID12792654
^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 PMID15098021