Evolution of enzyme functionality in the flavin-containing monooxygenases.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
24 02 2023
24 02 2023
Historique:
received:
14
09
2022
accepted:
15
02
2023
entrez:
23
2
2023
pubmed:
24
2
2023
medline:
3
3
2023
Statut:
epublish
Résumé
Among the molecular mechanisms of adaptation in biology, enzyme functional diversification is indispensable. By allowing organisms to expand their catalytic repertoires and adopt fundamentally different chemistries, animals can harness or eliminate new-found substances and xenobiotics that they are exposed to in new environments. Here, we explore the flavin-containing monooxygenases (FMOs) that are essential for xenobiotic detoxification. Employing a paleobiochemistry approach in combination with enzymology techniques we disclose the set of historical substitutions responsible for the family's functional diversification in tetrapods. Remarkably, a few amino acid replacements differentiate an ancestral multi-tasking FMO into a more specialized monooxygenase by modulating the oxygenating flavin intermediate. Our findings substantiate an ongoing premise that enzymatic function hinges on a subset of residues that is not limited to the active site core.
Identifiants
pubmed: 36823138
doi: 10.1038/s41467-023-36756-x
pii: 10.1038/s41467-023-36756-x
pmc: PMC9950137
doi:
Substances chimiques
dimethylaniline monooxygenase (N-oxide forming)
EC 1.14.13.8
Oxygenases
EC 1.13.-
Mixed Function Oxygenases
EC 1.-
Flavins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1042Informations de copyright
© 2023. The Author(s).
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