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Reverse Ordered Sequential Mechanism for Lactoperoxidase with Inhibition by Hydrogen Peroxide

Lactoperoxidase (LPO, Fe(III) in its resting state in the absence of substrates)—an enzyme secreted from human mammary, salivary, and other mucosal glands—catalyzes the oxidation of thiocyanate (SCN(−)) by hydrogen peroxide (H(2)O(2)) to produce hypothiocyanite (OSCN(−)), which functions as an antim...

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Detalles Bibliográficos
Autores principales: Cupp-Sutton, Kellye, Ashby, Michael T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8614691/
https://www.ncbi.nlm.nih.gov/pubmed/34829517
http://dx.doi.org/10.3390/antiox10111646
Descripción
Sumario:Lactoperoxidase (LPO, Fe(III) in its resting state in the absence of substrates)—an enzyme secreted from human mammary, salivary, and other mucosal glands—catalyzes the oxidation of thiocyanate (SCN(−)) by hydrogen peroxide (H(2)O(2)) to produce hypothiocyanite (OSCN(−)), which functions as an antimicrobial agent. The accepted catalytic mechanism, called the halogen cycle, comprises a two-electron oxidation of LPO by H(2)O(2) to produce oxoiron(IV) radicals, followed by O-atom transfer to SCN(−). However, the mechanism does not explain biphasic kinetics and inhibition by H(2)O(2) at low concentration of reducing substrate, conditions that may be biologically relevant. We propose an ordered sequential mechanism in which the order of substrate binding is reversed, first SCN(−) and then H(2)O(2). The sequence of substrate binding that is described by the halogen cycle mechanism is actually inhibitory.