Joel Sussman
Encyclopedia
Joel L. Sussman is an Israel
i crystallographer
best known for his studies on acetylcholinesterase
, a key protein involved in transmission of nerve signals. Born in Philadelphia, PA, he is the Morton and Gladys Pickman Professor of Structural Biology at the Weizmann Institute of Science, Rehovot
, ISRAEL and the Director of the Israel Structural Proteomics Center
Sussman’s current research focuses on nervous system proteins, especially acetylcholinesterase (AChE), whose 3D structure was first determined in his lab. This structure revealed [4-8]: (a) AChE is a prototype of the α/β hydrolase fold [4]; (b) π-cation interactions play a key role in binding of acetylcholine (ACh) and ligands to AChE [4]; (c) Its ACh-binding site assisted in structure-based design of promising leads for novel anti-Alzheimer’s drugs; (d) discovered a highly asymmetric charge distribution [5] conserved in ‘cholinesterase-like adhesion molecules’ (CLAMs), and showed that their cytoplasmic domains are ‘intrinsically unfolded’ [6] with implications for neural development and plasticity, and led to an algorithm, Foldindex©, for predicting whether a protein sequence will fold; (f) revealed a novel anchoring device for AChE involving superhelical assembly of its subunits around a polyproline-II helix [7]; and (g) illuminated 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 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 [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.
Israel
The State of Israel is a parliamentary republic located in the Middle East, along the eastern shore of the Mediterranean Sea...
i crystallographer
Crystallography
Crystallography is the experimental science of the arrangement of atoms in solids. The word "crystallography" derives from the Greek words crystallon = cold drop / frozen drop, with its meaning extending to all solids with some degree of transparency, and grapho = write.Before the development of...
best known for his studies on acetylcholinesterase
Acetylcholinesterase
"Acetylcholinesterase, also known as AChE or acetylcholine acetylhydrolase, is an enzyme that degrades the neurotransmitter acetylcholine, producing choline and an acetate group. It is mainly found at neuromuscular junctions and cholinergic nervous system, where its activity serves to terminate...
, a key protein involved in transmission of nerve signals. Born in Philadelphia, PA, he is the Morton and Gladys Pickman Professor of Structural Biology at the Weizmann Institute of Science, Rehovot
Rehovot
Rehovot is a city in the Center District of Israel, about south of Tel Aviv. According to the Israel Central Bureau of Statistics , at the end of 2009 the city had a total population of 112,700. Rehovot's official website estimates the population at 114,000.Rehovot was built on the site of Doron,...
, ISRAEL and the Director of the Israel Structural Proteomics Center
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 [4-8]: (a) AChE is a prototype of the α/β hydrolase fold [4]; (b) π-cation interactions play a key role in binding of acetylcholine (ACh) and ligands to AChE [4]; (c) Its ACh-binding site assisted in structure-based design of promising leads for novel anti-Alzheimer’s drugs; (d) discovered a highly asymmetric charge distribution [5] conserved in ‘cholinesterase-like adhesion molecules’ (CLAMs), and showed that their cytoplasmic domains are ‘intrinsically unfolded’ [6] with implications for neural development and plasticity, and led to an algorithm, Foldindex©, for predicting whether a protein sequence will fold; (f) revealed a novel anchoring device for AChE involving superhelical assembly of its subunits around a polyproline-II helix [7]; and (g) illuminated 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 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 [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.
Biographical information
- Formal education and training
- B.A. Cornell UniversityCornell UniversityCornell University is an Ivy League university located in Ithaca, New York, United States. It is a private land-grant university, receiving annual funding from the State of New York for certain educational missions...
(1965; Math & Physics) - PhD, MIT (1972; Biophysics, with Cyrus Levinthal)
- Postdoctoral research, Hebrew University (1972; with Yehuda Lapidot)
- Postdoctoral research, Duke University (1973; with Sung-Hou Kim)
- B.A. Cornell University
- Appointments and positions held
- 1976-80 Senior Scientists, Weizmann Institute of Science
- 1980-92 Associate Professor, Weizmann Institute of Science
- 1992-Now Professor, Weizmann Institute of Science
- 1984-85 Head, Dept of Structural Chemistry:
- 1988-89 Head, Kimmelman Center for Biomolecular Structure & Assembly
- 1994-99 Director, Protein Data Bank (PDB) at Brookhaven National Laboratory
- 2002-Now Incumbent of the Morton and Gladys Pickman Chair of Structural Biology
- Honors and awards
- 2005 Samuel and Paula Elkeles Prize for Outstanding Scientist in Medicine in Israel (together with Israel Silman)
- 2006 TEVA Founders Award for Breakthroughs in Molecular Medicine (together with H. Soreq and I. Silman)
- 2005 Honorary Professor Chinese Academy of Science
- 1994 Elected member EMBO (European Molecular Biology Organization)