This article may be too technical for most readers to understand.(August 2012) |
Joel Sussman | |
---|---|
Born | 24 September 1943 |
Nationality | Israeli |
Alma mater | Cornell University MIT Hebrew University |
Known for | Studies on acetylcholinesterase |
Awards | Samuel and Paula Elkeles Prize (2005) Teva Founders' Award (2006) |
Scientific career | |
Fields | Crystallography |
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.
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.
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.
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.
The enzyme cholinesterase (EC 3.1.1.8, choline esterase; systematic name acylcholine acylhydrolase) catalyses the hydrolysis of choline-based esters:
Galantamine is used for the treatment of cognitive decline in mild to moderate Alzheimer's disease and various other memory impairments. It is an alkaloid extracted from the bulbs and flowers of Galanthus nivalis, Galanthus caucasicus, Galanthus woronowii, and other members of the family Amaryllidaceae, such as Narcissus (daffodil), Leucojum aestivum (snowflake), and Lycoris including Lycoris radiata. It can also be produced synthetically.
Huperzine A is a naturally occurring sesquiterpene alkaloid compound found in the firmoss Huperzia serrata and in varying quantities in other food Huperzia species, including H. elmeri, H. carinat, and H. aqualupian. Huperzine A has been investigated as a treatment for neurological conditions such as Alzheimer's disease, but a meta-analysis of those studies concluded that they were of poor methodological quality and the findings should be interpreted with caution. Huperzine A inhibits the breakdown of the neurotransmitter acetylcholine by the enzyme acetylcholinesterase. It is commonly available over the counter as a nutrient supplement, and is marketed as a cognitive enhancer for improving memory and concentration.
Diisopropyl fluorophosphate (DFP) or Isoflurophate is an oily, colorless liquid with the chemical formula C6H14FO3P. It is used in medicine and as an organophosphorus insecticide. It is stable, but undergoes hydrolysis when subjected to moisture.
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).
Meir Wilchek is an Israeli biochemist. He is a professor at the Weizmann Institute of Science.
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.
Platelet-derived growth factor subunit A is a protein that in humans is encoded by the PDGFA gene.
Acetylcholinesterase (HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme that catalyzes the breakdown of acetylcholine and some other choline esters that function as neurotransmitters:
Carboxylesterase, type B is a family of evolutionarily related proteins that belongs to the superfamily of proteins with the Alpha/beta hydrolase fold.
The alpha/beta hydrolase superfamily is a superfamily of hydrolytic enzymes of widely differing phylogenetic origin and catalytic function that share a common fold. The core of each enzyme is an alpha/beta-sheet, containing 8 beta strands connected by 6 alpha helices. The enzymes are believed to have diverged from a common ancestor, retaining little obvious sequence similarity, but preserving the arrangement of the catalytic residues. All have a catalytic triad, the elements of which are borne on loops, which are the best-conserved structural features of the fold.
Guanine nucleotide-binding protein G(z) subunit alpha is a protein that in humans is encoded by the GNAZ gene.
Acetylcholinesterase collagenic tail peptide also known as AChE Q subunit, acetylcholinesterase-associated collagen, or ColQ is the collagen-tail subunit of acetylcholinesterase found in the neuromuscular junction. In humans it is encoded by the COLQ gene.
Olfactory receptor 51B5 is a protein that in humans is encoded by the OR51B5 gene.
Alkaline phosphatase, placental type also known as placental alkaline phosphatase (PLAP) is an allosteric enzyme that in humans is encoded by the ALPP gene.
Paraoxonases are a family of mammalian enzymes with aryldialkylphosphatase activity. There are three paraoxonase isozymes, which were originally discovered for their involvement in the hydrolysis of organophosphates.
Proteopedia is a wiki, 3D encyclopedia of proteins and other molecules. The site contains a page for every entry in the Protein Data Bank, as well as pages that are more descriptive of protein structures in general such as acetylcholinesterase, hemoglobin, and the photosystem II with a Jmol view that highlights functional sites and ligands. It employs a scene-authoring tool so that users do not have to learn JSmol script language to create customized molecular scenes. Custom scenes are easily attached to "green links" in descriptive text that display those scenes in JSmol. A web browser is all that is needed to access the site and the 3D information; no viewers are required to be installed.
Hermona Soreq is an Israeli professor of Molecular Neuroscience at The Hebrew University of Jerusalem. Best known for her work on the signaling of acetylcholine and its relevance in stress responses and neurodegenerative diseases such as Parkinson's and Alzheimer's.
Fasciculins are a class of toxic proteins found in certain snake venoms, notably some species of mamba. Investigations have revealed distinct forms in some green mamba venoms, in particular FAS1 and FAS2 Fasciculins are so called because they cause intense fasciculation in muscle fascicles of susceptible organisms, such as the preferred prey of the snakes. This effect helps to incapacitate the muscles, either killing the prey, or paralysing it so that the snake can swallow it.
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.