What Determines the Selectivity of Arginine Dihydroxylation by the Nonheme Iron Enzyme OrfP?


Journal

Chemistry (Weinheim an der Bergstrasse, Germany)
ISSN: 1521-3765
Titre abrégé: Chemistry
Pays: Germany
ID NLM: 9513783

Informations de publication

Date de publication:
21 Jan 2021
Historique:
received: 03 09 2020
revised: 22 09 2020
pubmed: 24 9 2020
medline: 27 2 2021
entrez: 23 9 2020
Statut: ppublish

Résumé

The nonheme iron enzyme OrfP reacts with l-Arg selectively to form the 3R,4R-dihydroxyarginine product, which in mammals can inhibit the nitric oxide synthase enzymes involved in blood pressure control. To understand the mechanisms of dioxygen activation of l-Arg by OrfP and how it enables two sequential oxidation cycles on the same substrate, we performed a density functional theory study on a large active site cluster model. We show that substrate binding and positioning in the active site guides a highly selective reaction through C

Identifiants

pubmed: 32965733
doi: 10.1002/chem.202004019
doi:

Substances chimiques

Nonheme Iron Proteins 0
Hydrogen 7YNJ3PO35Z
Arginine 94ZLA3W45F

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1795-1809

Informations de copyright

© 2020 Wiley-VCH GmbH.

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Auteurs

Hafiz Saqib Ali (HS)

Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
Department of Chemistry, The University of Manchester, Oxford Road, Manchester, M13 9PL, UK.

Richard H Henchman (RH)

Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
Department of Chemistry, The University of Manchester, Oxford Road, Manchester, M13 9PL, UK.

Sam P de Visser (SP)

Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
Department of Chemical Engineering and Analytical Science, The University of Manchester, Oxford Road, Manchester, M13 9PL, UK.

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