Abstract

Flavin-dependent monooxygenases must stabilize a C4a-hydroperoxyflavin intermediate to hydroxylate their respective substrates. Formation and decay of the C4a-hydroperoxyflavin were monitored under rapid reaction kinetic conditions in SidA, an N-hydroxylating monooxygenase involved in siderophore biosynthesis. Solvent kinetic isotope effect studies of flavin oxidation indicate that both hydrogen peroxide elimination and water elimination occur via abstraction of hydrogen from the N5 of the flavin. Kinetic isotope effect and density functional theory results are consistent with the transfer of a proton from the 2′-OH of the nicotinamide ribose of nicotinamide adenine dinucleotide phosphate (NADP+) to the C4a-peroxyflavin to form the C4a-hydroperoxyflavin. This represents a novel role for NADP+ in the reaction of flavin-dependent enzymes. © 2013 American Chemical Society.

Department(s)

Chemistry

Comments

National Science Foundation, Grant 1021384

International Standard Serial Number (ISSN)

1520-4995; 0006-2960

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2024 American Chemical Society, All rights reserved.

Publication Date

23 Dec 2013

PubMed ID

24321106

Included in

Chemistry Commons

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