New frontiers in flavin-dependent monooxygenases.
Antibiotics
Conformational changes
Drug target
Flavin motions
Homolytic bond cleavage
Monooxygenation
Oxygen activation
Journal
Archives of biochemistry and biophysics
ISSN: 1096-0384
Titre abrégé: Arch Biochem Biophys
Pays: United States
ID NLM: 0372430
Informations de publication
Date de publication:
15 03 2021
15 03 2021
Historique:
received:
12
11
2020
revised:
08
01
2021
accepted:
11
01
2021
pubmed:
19
1
2021
medline:
26
3
2021
entrez:
18
1
2021
Statut:
ppublish
Résumé
Flavin-dependent monooxygenases catalyze a wide variety of redox reactions in important biological processes and are responsible for the synthesis of highly complex natural products. Although much has been learned about FMO chemistry in the last ~80 years of research, several aspects of the reactions catalyzed by these enzymes remain unknown. In this review, we summarize recent advancements in the flavin-dependent monooxygenase field including aspects of flavin dynamics, formation and stabilization of reactive species, and the hydroxylation mechanism. Novel catalysis of flavin-dependent N-oxidases involving consecutive oxidations of amines to generate oximes or nitrones is presented and the biological relevance of the products is discussed. In addition, the activity of some FMOs have been shown to be essential for the virulence of several human pathogens. We also discuss the biomedical relevance of FMOs in antibiotic resistance and the efforts to identify inhibitors against some members of this important and growing family enzymes.
Identifiants
pubmed: 33460580
pii: S0003-9861(21)00015-1
doi: 10.1016/j.abb.2021.108765
pii:
doi:
Substances chimiques
Enzyme Inhibitors
0
Flavins
0
Flavoproteins
0
Mixed Function Oxygenases
EC 1.-
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
108765Informations de copyright
Copyright © 2021. Published by Elsevier Inc.