title: Control of oxidative posttranslational cysteine modifications: from intricate chemistry to widespread biological and medical applications.
abstract: Cysteine residues in proteins and enzymes often fulfill rather important roles, particularly in the context of cellular signaling, protein-protein interactions, substrate and metal binding, and catalysis. At the same time, some of the most active cysteine residues are also quite sensitive toward (oxidative) modification. S-Thiolation, S-nitrosation, and disulfide bond and sulfenic acid formation are processes which occur frequently inside the cell and regulate the function and activity of many proteins and enzymes. During oxidative stress, such modifications trigger, among others, antioxidant responses and cell death. The unique combination of nonredox function on the one hand and participation in redox signaling and control on the other has placed many cysteine proteins at the center of drug design and pesticide development. Research during the past decade has identified a range of chemically rather interesting, biologically very active substances that are able to modify cysteine residues in such proteins with huge efficiency, yet also considerable selectivity. These agents are often based on natural products and range from simple disulfides to complex polysulfanes, tetrahydrothienopyridines, α,β -unsaturated disulfides, thiuramdisulfides, and 1,2-dithiole-3-thiones. At the same time, inhibition of enzymes responsible for posttranslational cysteine modifications (and their removal) has become an important area of innovative drug research. Such investigations into the control of the cellular thiolstat by thiol-selective agents cross many disciplines and are often far from trivial.
authors: Division of Bioorganic Chemistry, School of Pharmacy, Saarland University, D-66123 Saarbruecken, Germany. c.jacob@mx.uni-saarland.de
authors: Claus
authors: C
authors: Jacob
authors: Eric
authors: E
authors: Battaglia
authors: Torsten
authors: T
authors: Burkholz
authors: Du
authors: D
authors: Peng
authors: Denyse
authors: D
authors: Bagrel
authors: Mathias
authors: M
authors: Montenarh
mesh_terms: D003545:Cysteine / Q000378:metabolism*; D004220:Disulfides / Q000378:metabolism; D006801:Humans; D010084:Oxidation-Reduction; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000378:metabolism*; D013456:Sulfur Acids / Q000378:metabolism
chemical_list: D004220:Disulfides; D011506:Proteins; D013456:Sulfur Acids; D003545:Cysteine