Abstract

Flavin-dependent monooxygenases (FMOs) constitute a diverse enzyme family that catalyzes crucial hydroxylation, epoxidation, and Baeyer–Villiger reactions across various metabolic pathways in all domains of life. Due to the intricate nature of this enzyme family's mechanisms, some aspects of their functioning remain unknown. Here, we present the results of molecular dynamics computations, supplemented by a bioinformatics analysis, that clarify the early stages of their catalytic cycle. We have elucidated the intricate binding mechanism of NADPH and L-Orn to a class B monooxygenase, the ornithine hydroxylase from (Formula presented.) (Formula presented.) known as SidA. Our investigation involved a comprehensive characterization of the conformational changes associated with the FAD (Flavin Adenine Dinucleotide) cofactor, transitioning from the out to the in position. Furthermore, we explored the rotational dynamics of the nicotinamide ring of NADPH, shedding light on its role in facilitating FAD reduction, supported by experimental evidence. Finally, we also analyzed the extent of conservation of two Tyr-loops that play critical roles in the process.

Department(s)

Chemistry

Publication Status

Full Access

Comments

Consejo Nacional de Investigaciones Científicas y Técnicas, Grant 11220130100260CO

Keywords and Phrases

flavin dynamics; flavin-dependent monooxygenases; NADPH binding; NADPH dynamics; ornithine binding; uncoupling

International Standard Serial Number (ISSN)

1469-896X; 0961-8368

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2024 Wiley, All rights reserved.

Publication Date

01 Apr 2024

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Chemistry Commons

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