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DOI10.1073/pnas.2012591118
A shared mechanistic pathway for pyridoxal phosphate–dependent arginine oxidases
Hoffarth E.R.; Haatveit K.C.; Kuatsjah E.; MacNeil G.A.; Saroya S.; Walsby C.J.; Eltis L.D.; Houk K.N.; Garcia-Borràs M.; Ryan K.S.
发表日期2021
ISSN0027-8424
卷号118期号:40
英文摘要The mechanism by which molecular oxygen is activated by the organic cofactor pyridoxal phosphate (PLP) for oxidation reactions remains poorly understood. Recent work has identified arginine oxidases that catalyze desaturation or hydroxylation reactions. Here, we investigate a desaturase from the Pseudoalteromonas luteoviolacea indolmycin pathway. Our work, combining X-ray crystallographic, biochemical, spectroscopic, and computational studies, supports a shared mechanism with arginine hydroxylases, involving two rounds of single-electron transfer to oxygen and superoxide rebound at the 4′ carbon of the PLP cofactor. The precise positioning of a water molecule in the active site is proposed to control the final reaction outcome. This proposed mechanism provides a unified framework to understand how oxygen can be activated by PLP-dependent enzymes for oxidation of arginine and elucidates a shared mechanistic pathway and intertwined evolutionary history for arginine desaturases and hydroxylases. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Molecular dynamics; Oxidase; Pyridoxal phosphate; Water; X-ray crystallography
语种英语
scopus关键词arginine oxidase; carbon; oxidoreductase; pyridoxal 5 phosphate; unclassified drug; Article; biochemical analysis; crystal structure; electron transport; enzyme active site; enzyme activity; mutagenesis; nonhuman; oxidation; Pseudoalteromonas; Pseudoalteromonas luteoviolacea; sequence homology; X ray crystallography
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/238363
作者单位Department of Chemistry, University of British Columbia, Vancouver, BC V6T 1Z1, Canada; Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA 90095, United States; Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Department of Chemistry, Simon Fraser University, Burnaby, BC V5A 1S6, Canada; Institute of Computational Chemistry and Catalysis, University of Girona, Girona, 17003, Spain; Department of Chemistry, University of Girona, Girona, 17003, Spain; Renewable Resources and Enabling Sciences Center, National Renewable Energy Laboratory, Golden, CO 80401, United States
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Hoffarth E.R.,Haatveit K.C.,Kuatsjah E.,等. A shared mechanistic pathway for pyridoxal phosphate–dependent arginine oxidases[J],2021,118(40).
APA Hoffarth E.R..,Haatveit K.C..,Kuatsjah E..,MacNeil G.A..,Saroya S..,...&Ryan K.S..(2021).A shared mechanistic pathway for pyridoxal phosphate–dependent arginine oxidases.Proceedings of the National Academy of Sciences of the United States of America,118(40).
MLA Hoffarth E.R.,et al."A shared mechanistic pathway for pyridoxal phosphate–dependent arginine oxidases".Proceedings of the National Academy of Sciences of the United States of America 118.40(2021).
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