Suicide inhibition
In biochemistry, suicide inhibition, also known as suicide inactivation or mechanism-based inhibition, is an irreversible form of enzyme inhibition that occurs when an enzyme binds a substrate analog and forms an irreversible complex with it through a covalent bond during the normal catalysis reaction. The inhibitor binds to the active site where it is modified by the enzyme to produce a reactive group that reacts irreversibly to form a stable inhibitor-enzyme complex. This usually uses a prosthetic group or a coenzyme, forming electrophilic alpha and beta unsaturated carbonyl compounds and imines. Examples Some clinical examples of suicide inhibitors include: Disulfiram, which inhibits the acetaldehyde dehydrogenase enzyme. Aspirin, which inhibits cyclooxygenase 1 and 2 enzymes. Clavulanic acid, which inhibits β-lactamase: clavulanic acid covalently bonds to a serine residue in the active site of the β-lactamase, restructuring the clavulanic acid molecule, creating a much more reactive species that attacks another amino acid in the active site, permanently inactivating it, and thus inactivating the enzyme β-lactamase. Penicillin, which inhibits DD-transpeptidase from building bacterial cell walls. Sulbactam, which prohibits penicillin-resistant strains of bacteria from metabolizing penicillin. AZT (zidovudine) and other chain-terminating nucleoside analogues used to inhibit HIV-1 reverse transcriptase in the treatment of HIV/AIDS.