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DOI | 10.1073/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 |
ISSN | 0027-8424 |
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 |
推荐引用方式 GB/T 7714 | 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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