Cysteine regulation of protein function--as exemplified by NMDA-receptor modulation.
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Lipton SA, Choi YB, Takahashi H, Zhang D, Li W, Godzik A, Bankston LA
Cysteine regulation of protein function--as exemplified by NMDA-receptor modulation.
Trends Neurosci. 2002 Sep;25(9):474-80.
- PubMed ID
- 12183209 [ View in PubMed]
- Abstract
Until recently cysteine residues, especially those located extracellularly, were thought to be important for metal coordination, catalysis and protein structure by forming disulfide bonds - but they were not thought to regulate protein function. However, this is not the case. Crucial cysteine residues can be involved in modulation of protein activity and signaling events via other reactions of their thiol (sulfhydryl; -SH) groups. These reactions can take several forms, such as redox events (chemical reduction or oxidation), chelation of transition metals (chiefly Zn(2+), Mn(2+) and Cu(2+)) or S-nitrosylation [the catalyzed transfer of a nitric oxide (NO) group to a thiol group]. In several cases, these disparate reactions can compete with one another for the same thiol group on a single cysteine residue, forming a molecular switch composed of a latticework of possible redox, NO or Zn(2+) modifications to control protein function. Thiol-mediated regulation of protein function can also involve reactions of cysteine residues that affect ligand binding allosterically. This article reviews the basis for these molecular cysteine switches, drawing on the NMDA receptor as an exemplary protein, and proposes a molecular model for the action of S-nitrosylation based on recently derived crystal structures.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Acetylcysteine Glutamate receptor ionotropic, NMDA 1 Protein Humans UnknownActivatorDetails Acetylcysteine Glutamate receptor ionotropic, NMDA 2A Protein Humans UnknownActivatorDetails Acetylcysteine Glutamate receptor ionotropic, NMDA 2B Protein Humans UnknownActivatorDetails Acetylcysteine Glutamate receptor ionotropic, NMDA 2D Protein Humans UnknownActivatorDetails Acetylcysteine Glutamate receptor ionotropic, NMDA 3A Protein Humans UnknownActivatorDetails