title: A comparison of reversible versus irreversible protein glutathionylation.
abstract: Glutathionylation is generally a reversible posttranslational modification that occurs to cysteine residues that have been exposed to reactive oxygen species (P-SSG). This cyclical process can regulate various clusters of proteins, including those involved in critical cellular signaling functions. However, certain conditions can favor the formation of dehydroamino acids, such as 2,3-didehydroalanine (2,3-dehydroalanine, DHA) and 2,3-didehydrobutyrine (2,3-dehydrobutyrine), which can act as Michael acceptors. In turn, these can form Michael adducts with glutathione (GSH), resulting in the formation of a stable thioether conjugate, an irreversible process referred to as nonreducible glutathionylation. This is predicted to be prevalent in nature, particularly in more slowly turning over proteins. Such nonreducible glutathionylation can be distinguished from the more facile cycling signaling processes and is predicted to be of gerontological, toxicological, pharmacological, and oncological relevance. Here, we compare reversible and irreversible glutathionylation.
authors: Department of Pharmaceutical and Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.
authors: Danyelle M
authors: DM
authors: Townsend
authors: Department of Biochemistry and Biotechnology, Vassyl Stefanyk Precarpathian National University, Ivano-Frankivsk, Ukraine.
authors: Volodymyr I
authors: VI
authors: Lushchak
authors: Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York, USA. Electronic address: arthur_cooper@nymc.edu.
authors: Arthur J L
authors: AJ
authors: Cooper
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry; D000613:Aminobutyrates / Q000737:chemistry*; D004798:Enzymes / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D054477:Glutaredoxins / Q000737:chemistry; D005978:Glutathione / Q000737:chemistry* / Q000502:physiology*; D019803:Glutathione Disulfide; D005982:Glutathione Transferase / Q000737:chemistry*; D006801:Humans; D007908:Lens, Crystalline / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*; D017382:Reactive Oxygen Species; D015398:Signal Transduction
chemical_list: D000613:Aminobutyrates; D004798:Enzymes; D054477:Glutaredoxins; D010455:Peptides; D011506:Proteins; D017382:Reactive Oxygen Species; C088694:dehydrobutyrine; C015102:dehydroalanine; D005982:Glutathione Transferase; D005978:Glutathione; D000409:Alanine; D019803:Glutathione Disulfide
keywords: Dehydroalanine; Glutaredoxin; Glutathione; Glutathione S-transferases; Glutathione disulfide; Irreversible protein glutathionylation; Lanthionine; Reversible glutathionylation; γ-Glutamyl-L-cysteine