Catalytic site flexibility facilitates the substrate and catalytic promiscuity of Vibrio dual lipase/transferase.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
09 08 2023
09 08 2023
Historique:
received:
26
01
2023
accepted:
27
07
2023
medline:
11
8
2023
pubmed:
10
8
2023
entrez:
9
8
2023
Statut:
epublish
Résumé
Although enzyme catalysis is typified by high specificity, enzymes can catalyze various substrates (substrate promiscuity) and/or different reaction types (catalytic promiscuity) using a single active site. This interesting phenomenon is widely distributed in enzyme catalysis, with both fundamental and applied importance. To date, the mechanistic understanding of enzyme promiscuity is very limited. Herein, we report the structural mechanism underlying the substrate and catalytic promiscuity of Vibrio dual lipase/transferase (VDLT). Crystal structures of the VDLT from Vibrio alginolyticus (ValDLT) and its fatty acid complexes were solved, revealing prominent structural flexibility. In particular, the "Ser-His-Asp" catalytic triad machinery of ValDLT contains an intrinsically flexible oxyanion hole. Analysis of ligand-bound structures and mutagenesis showed that the flexible oxyanion hole and other binding residues can undergo distinct conformational changes to facilitate substrate and catalytic promiscuity. Our study reveals a previously unknown flexible form of the famous catalytic triad machinery and proposes a "catalytic site tuning" mechanism to expand the mechanistic paradigm of enzyme promiscuity.
Identifiants
pubmed: 37558668
doi: 10.1038/s41467-023-40455-y
pii: 10.1038/s41467-023-40455-y
pmc: PMC10412561
doi:
Substances chimiques
Lipase
EC 3.1.1.3
Transferases
EC 2.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4795Informations de copyright
© 2023. Springer Nature Limited.
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