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.
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 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
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
^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. USA90, 5128-5132
PMID8506359
^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