Evidence for a thiol reagent inhibiting choline acetyltransferase by reacting with the thiol group of coenzyme a forming a potent inhibitor

Acetyl-coenzyme A and coenzyme A analogues. Their effects on rat brain choline acetyltransferase

“…In vertebrates, the ratio between CoA K1 value and acetyl-CoA Km value is about 1. With squid optic lobes enzyme, this ratio is close to 200 (acetyl-CoA Ki,, 48pM; CoA K1, 7500pM) (Currier & Mautner, 1976).…”

“…I have also tested on the rat brain enzyme the mixed CoA disulphides prepared in the laboratory (Currier & Mautner, 1976). These compounds, CoAS-SMe and its analogues CoAS-SEt and CoAS-SPr, were better inhibitors than CoA itself.…”

Advances in the Research of β-Ketoacyl-ACP Synthase III (FabH) Inhibitors

“…Alkyl-CoA disulfides have been used previously as inhibitors and probes of choline acetyl transferase [43,44,45,46,47,48] and spermidine/spermine acetyl transferases [49]. Currier and Mautner demonstrated that methyl-CoA disulfide is a potent competitive inhibitor of choline acetyl transferase, and they proposed that the methyl-CoA disulfide (MeSS-CoA) forms a tight complex with the enzyme without undergoing chemical reaction [43,44].…”

“…Currier and Mautner demonstrated that methyl-CoA disulfide is a potent competitive inhibitor of choline acetyl transferase, and they proposed that the methyl-CoA disulfide (MeSS-CoA) forms a tight complex with the enzyme without undergoing chemical reaction [43,44]. Mamoun M. Alhamadsheh et al hypothesized that alkyl-CoA disulfides should act as FabH inhibitors through formation of a mixed disulfide with the active site Cys112, if the pKa of the cysteine-SH group is low enough.…”

Structural and dynamical aspects of Streptococcus gordonii FabH through molecular docking and MD simulations

“…The best hit, methyl-CoA disulfide has also been reported to be a potent competitive inhibitor of choline acetyltransferase by Currier and Mautner. Currier and Maunter proposed that the methyl-CoA disulfide forms a tight complex with the enzyme by reaction with thiol group of CoA[79,80]. Critical evaluation of the nature of binding interaction of methyl-CoA disulfide revealed very strong contacts with the following protein residues Asp219, CoA disulfide bound compactly at the binding tunnel of FabH.…”