Joel Sussman

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. Born in Philadelphia, he is the Morton and Gladys Pickman Professor of Structural Biology at the Weizmann Institute of Science in Rehovot and the director of the Israel Structural Proteomics Center there.

Formal education and training

In 1965, Sussman got his B.A. at the Cornell University in math and physics. He got his PhD from MIT in biophysics in 1972 with Cyrus Levinthal. Sussman later did 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 held the following positions at the Weizmann Institute of Science:

• 1976–80 – Senior Scientist
• 1980–92 – Associate Professor
• 1992–date – Professor
• 1984–85 – Head, Department of Structural Chemistry
• 1988–89 – Head, Kimmelman Center for Biomolecular Structure and Assembly
• 2002–date – Incumbent of the Morton and Gladys Pickman Chair of Structural Biology

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] He subsequently determined the structures of 'bulge'-containing DNA fragments as models for insertion mutations.^[2]

Sussman's current research focuses on nervous system proteins, especially acetylcholinesterase (AChE), whose 3D structure was first determined in his lab. This structure revealed:^{[3][4][5][6][7]}

• AChE is a prototype of the α/β hydrolase fold;^[3]
• π-cation interactions play a key role in binding of acetylcholine (ACh) and ligands to AChE;^[3]
• Its ACh-binding site assisted in structure-based design of promising leads for novel anti-Alzheimer's drugs;
• Discovered a highly asymmetric charge distribution^[4] conserved in 'cholinesterase-like adhesion molecules' (CLAMs), and showed that their cytoplasmic domains are 'intrinsically unfolded'^[5] with implications for neural development and plasticity, and led to an algorithm, ^[8] for predicting whether a protein sequence will fold;
• A novel anchoring device for AChE involving superhelical assembly of its subunits around a polyproline-II helix;^[6]
• 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 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.

Honors and awards

• 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)

References

External links

• Prof. Sussman at the Weizmann Institute
• The Israel Structural Proteomics Center