Protein cysteine CoAlation (CoAlation) (CoAlation)

Protein CoAlation is a reversible post-translational modification (PTM) where Coenzyme A (CoA) forms a covalent disulfide bond with specific cysteine residues on proteins, primarily during oxidative or metabolic stress (Gout, 2018, Biochemical Society Transactions). This modification serves a dual purpose: it protects critical protein thiols from irreversible over-oxidation to sulfinic or sulfonic acids and regulates the activity of various metabolic and signaling proteins (Tsuchiya et al., 2017, Biochemical Journal). The process is highly dynamic and is reversed by de-CoAlating enzymes, such as Nudix hydrolases (e.g., NUDT7 and NUDT15), which cleave the CoA-protein bond (Baković et al., 2019, Free Radical Biology and Medicine). Research has identified a wide range of CoAlated proteins, termed the "CoAlome," which includes key enzymes in glycolysis, the TCA cycle, and antioxidant defense, effectively linking cellular metabolism with redox status (Malanchuk et al., 2021, Monoclonal Antibodies in Immunodiagnosis and Immunotherapy). While no clinical drugs currently target this process directly, the modulation of de-CoAlating enzymes or cellular CoA levels represents a promising therapeutic strategy for diseases associated with oxidative stress, such as cancer, neurodegeneration, and ischemia-reperfusion injury.

Other names

S-CoAlationProtein S-CoAlationCoenzyme A-lationCovalent CoA-protein adducts

Reversible covalent modification of cysteine thiols by Coenzyme A to protect against irreversible oxidation and regulate enzymatic activity.