Joel Sussman

Last updated
Joel Sussman
Born (1943-09-24) 24 September 1943 (age 79)
NationalityIsraeli
Alma mater Cornell University
MIT
Hebrew University
Known forStudies on acetylcholinesterase
AwardsSamuel and Paula Elkeles Prize (2005)
Teva Founders' Award (2006)
Scientific career
FieldsCrystallography
Institutions Weizmann Institute of Science

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.

Contents

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.

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] [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:

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

Related Research Articles

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The enzyme cholinesterase (EC 3.1.1.8, choline esterase; systematic name acylcholine acylhydrolase) catalyses the hydrolysis of choline-based esters:

<span class="mw-page-title-main">Galantamine</span> Neurological medication

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<span class="mw-page-title-main">Huperzine A</span> Chemical compound

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<span class="mw-page-title-main">G protein-coupled receptor kinase 2</span> Enzyme

G-protein-coupled receptor kinase 2 (GRK2) is an enzyme that in humans is encoded by the ADRBK1 gene. GRK2 was initially called Beta-adrenergic receptor kinase, and is a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinases that is most highly similar to GRK3(βARK2).

<span class="mw-page-title-main">Meir Wilchek</span> Israeli biochemist (born 1935)

Meir Wilchek is an Israeli biochemist. He is a professor at the Weizmann Institute of Science.

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Serum paraoxonase and arylesterase 1 (PON1) also known as A esterase , homocysteine thiolactonase or serum aryldialkylphosphatase 1 is an enzyme that in humans is encoded by the PON1 gene. Paraoxonase 1 has esterase and more specifically paraoxonase activity. PON1 is the first discovered member of a multigene family also containing PON2 and PON3, the genes for which are located adjacent to each other on chromosome 7. It has recently been shown that PON1 on HDL is responsible for significant atheroprotection rendered by the HDL.

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<span class="mw-page-title-main">Fasciculin</span> Class of toxins found in some snake venoms

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<span class="mw-page-title-main">TMTFA</span> Chemical compound

TMTFA is an extremely potent acetylcholinesterase inhibitor. As a transition state analog of acetylcholinesterase, TMTFA is able to inhibit acetylcholinesterase at extremely low concentrations, making it one of the most potent acetylcholinesterase inhibitors known.

References

  1. 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. PMID   775636.
  2. 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. doi:10.1107/S0567739477001958.
  3. 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 PMID   3386751
  4. 1 2 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" Science253, 872-879. PMID   1678899
  5. 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 PMID   8506359
  6. 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 PMID   14579366
  7. 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. PMID   10639129
  8. Dym, O.; Mevarech, M.; Sussman, J.L. (1995). "Structural features that stabilize Halophilic malate dehydrogenase from an Archaebacterium". Science. 267 (5202): 1344–1346. doi:10.1126/science.267.5202.1344. PMID   17812611. S2CID   20750377.
  9. 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 PMID   15894606
  10. 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 PMID   12792654
  11. 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 PMID   15098021