Mixed and non-competitive enzyme inhibition: underlying mechanisms and mechanistic irrelevance of the formal two-site model.
Mixed inhibition
inhibition mechanism
non-competitive inhibition
Journal
Journal of enzyme inhibition and medicinal chemistry
ISSN: 1475-6374
Titre abrégé: J Enzyme Inhib Med Chem
Pays: England
ID NLM: 101150203
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
medline:
15
8
2023
pubmed:
14
8
2023
entrez:
14
8
2023
Statut:
ppublish
Résumé
The formal mechanism of linear mixed and non-competitive enzyme inhibition implies the binding of inhibitors to both the active site of the free enzyme in competition with the substrate, and to an allosteric site on the enzyme-substrate complex. However, it is evident from a review of the scientific literature that the two-site mechanism is frequently mistaken as the actual underlying mechanism of mixed inhibition. In this study, we conducted a comprehensive assessment of the mechanistic relevance of this type of inhibition using a statistical approach. By combining a statistical analysis of the inhibition cases documented in the BRENDA database with a theoretical investigation of inhibition models, we conclude that mixed inhibitors exclusively bind to the active site of enzymes. Hence ruling out any implication of allosteric sites and depriving the two-site model of any mechanistic relevance.
Identifiants
pubmed: 37577806
doi: 10.1080/14756366.2023.2245168
pmc: PMC10683834
doi:
Substances chimiques
Enzyme Inhibitors
0
Types de publication
Review
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2245168Références
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