Reverse Ordered Sequential Mechanism for Lactoperoxidase with Inhibition by Hydrogen Peroxide

Lactoperoxidase (LPO, FeIII 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 (H2O<sub...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Kellye Cupp-Sutton, Michael T. Ashby
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	lactoperoxidase thiocyanate kinetics mechanism Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/b6693e4545d24db69cbb3807a9b74354
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b6693e4545d24db69cbb3807a9b74354
record_format	dspace
spelling	oai:doaj.org-article:b6693e4545d24db69cbb3807a9b743542021-11-25T16:25:17ZReverse Ordered Sequential Mechanism for Lactoperoxidase with Inhibition by Hydrogen Peroxide10.3390/antiox101116462076-3921https://doaj.org/article/b6693e4545d24db69cbb3807a9b743542021-10-01T00:00:00Zhttps://www.mdpi.com/2076-3921/10/11/1646https://doaj.org/toc/2076-3921Lactoperoxidase (LPO, Fe<sup>III</sup> 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<sup>−</sup>) by hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) to produce hypothiocyanite (OSCN<sup>−</sup>), which functions as an antimicrobial agent. The accepted catalytic mechanism, called the halogen cycle, comprises a two-electron oxidation of LPO by H<sub>2</sub>O<sub>2</sub> to produce oxoiron(IV) radicals, followed by O-atom transfer to SCN<sup>−</sup>. However, the mechanism does not explain biphasic kinetics and inhibition by H<sub>2</sub>O<sub>2</sub> 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<sup>−</sup> and then H<sub>2</sub>O<sub>2</sub>. The sequence of substrate binding that is described by the halogen cycle mechanism is actually inhibitory.Kellye Cupp-SuttonMichael T. AshbyMDPI AGarticlelactoperoxidasethiocyanatekineticsmechanismTherapeutics. PharmacologyRM1-950ENAntioxidants, Vol 10, Iss 1646, p 1646 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	lactoperoxidase thiocyanate kinetics mechanism Therapeutics. Pharmacology RM1-950
spellingShingle	lactoperoxidase thiocyanate kinetics mechanism Therapeutics. Pharmacology RM1-950 Kellye Cupp-Sutton Michael T. Ashby Reverse Ordered Sequential Mechanism for Lactoperoxidase with Inhibition by Hydrogen Peroxide
description	Lactoperoxidase (LPO, Fe<sup>III</sup> 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<sup>−</sup>) by hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) to produce hypothiocyanite (OSCN<sup>−</sup>), which functions as an antimicrobial agent. The accepted catalytic mechanism, called the halogen cycle, comprises a two-electron oxidation of LPO by H<sub>2</sub>O<sub>2</sub> to produce oxoiron(IV) radicals, followed by O-atom transfer to SCN<sup>−</sup>. However, the mechanism does not explain biphasic kinetics and inhibition by H<sub>2</sub>O<sub>2</sub> 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<sup>−</sup> and then H<sub>2</sub>O<sub>2</sub>. The sequence of substrate binding that is described by the halogen cycle mechanism is actually inhibitory.
format	article
author	Kellye Cupp-Sutton Michael T. Ashby
author_facet	Kellye Cupp-Sutton Michael T. Ashby
author_sort	Kellye Cupp-Sutton
title	Reverse Ordered Sequential Mechanism for Lactoperoxidase with Inhibition by Hydrogen Peroxide
title_short	Reverse Ordered Sequential Mechanism for Lactoperoxidase with Inhibition by Hydrogen Peroxide
title_full	Reverse Ordered Sequential Mechanism for Lactoperoxidase with Inhibition by Hydrogen Peroxide
title_fullStr	Reverse Ordered Sequential Mechanism for Lactoperoxidase with Inhibition by Hydrogen Peroxide
title_full_unstemmed	Reverse Ordered Sequential Mechanism for Lactoperoxidase with Inhibition by Hydrogen Peroxide
title_sort	reverse ordered sequential mechanism for lactoperoxidase with inhibition by hydrogen peroxide
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/b6693e4545d24db69cbb3807a9b74354
work_keys_str_mv	AT kellyecuppsutton reverseorderedsequentialmechanismforlactoperoxidasewithinhibitionbyhydrogenperoxide AT michaeltashby reverseorderedsequentialmechanismforlactoperoxidasewithinhibitionbyhydrogenperoxide
_version_	1718413221933613056

Reverse Ordered Sequential Mechanism for Lactoperoxidase with Inhibition by Hydrogen Peroxide

Ejemplares similares