Abstract 1186 Regulation of stereospecificity of the hydride transfer step in class B flavin-dependent monooxygenases
Year: 2024
Type: conference-abstract
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. The complex nature of this enzyme family's mechanisms of action contributes to numerous unknown aspects of their functioning. Here, we present the results of Molecular Dynamics computations, supplemented by 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 Siderophore A from Aspergillus fumigatus. Our investigation involved a comprehensive analysis 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 This research was supported in part by National Science Foundation grants CHE-2003658 (to P.S). Universidad Nacional de Quilmes (UNQ) (ID:1292/19), ANPCyT (PICT 2020-SerieA-00192), CONICET (ID:11220130100260CO) and Fulbright.
Source: Journal of Biological Chemistry
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,800
Awards: Estudios experimentales y teóricos sobre los mecanismos moleculares del funcionamiento de canales y transportadores trans-membrana, G3297509091, Collaborative Research: Structure and function of flavin-dependent N-monooxygenases, G4328314451, G4856265916, G5372344251, G727479675, G7378882120
OpenAlex ID: W4393139256