Identification of Protein Targets of S-Nitroso-Coenzyme A-Mediated S-Nitrosation Using Chemoproteomics. ACS Chem Biol 2024 Jan 19;19(1):193-207
Date
01/02/2024Pubmed ID
38159293DOI
10.1021/acschembio.3c00654Scopus ID
2-s2.0-85181803360 (requires institutional sign-in at Scopus site)Abstract
S-Nitrosation is a cysteine post-translational modification fundamental to cellular signaling. This modification regulates protein function in numerous biological processes in the nervous, cardiovascular, and immune systems. Small molecule or protein nitrosothiols act as mediators of NO signaling by transferring the NO group (formally NO+) to a free thiol on a target protein through a transnitrosation reaction. The protein targets of specific transnitrosating agents and the extent and functional effects of S-nitrosation on these target proteins have been poorly characterized. S-nitroso-coenzyme A (CoA-SNO) was recently identified as a mediator of endogenous S-nitrosation. Here, we identified direct protein targets of CoA-SNO-mediated transnitrosation using a competitive chemical-proteomic approach that quantified the extent of modification on 789 cysteine residues in response to CoA-SNO. A subset of cysteines displayed high susceptibility to modification by CoA-SNO, including previously uncharacterized sites of S-nitrosation. We further validated and functionally characterized the functional effects of S-nitrosation on the protein targets phosphofructokinase (platelet type), ATP citrate synthase, and ornithine aminotransferase.
Author List
Falco JA, Wynia-Smith SL, McCoy J, Smith BC, Weerapana EAuthors
Brian C. Smith PhD Associate Professor in the Biochemistry department at Medical College of WisconsinSarah L. Wynia Smith Research Scientist I in the Biochemistry department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Coenzyme ACysteine
Nitric Oxide
Nitrosation
Proteins
Proteomics
S-Nitrosothiols
