8H0B

Structure of the thermolabile hemolysin from Vibrio alginolyticus (in complex with oleic acid)

Summary for 8H0B

• Entry DOI: 10.2210/pdb8h0b/pdb
• Descriptor: SGNH/GDSL hydrolase family protein, OLEIC ACID, PENTAETHYLENE GLYCOL, ... (5 entities in total)
• Functional Keywords: vibrio, phospholipase, sgnh hydrolase, gdsl lipase, transferase, thermolabile hemolysin, hydrolase
• Biological source: Vibrio alginolyticus
• Total number of polymer chains: 2
• Total formula weight: 97302.54

Authors

Ma, Q.,Wang, C. (deposition date: 2022-09-28, release date: 2023-08-16)

Primary citation

Wang, C.,Liu, C.,Zhu, X.,Peng, Q.,Ma, Q.
Catalytic site flexibility facilitates the substrate and catalytic promiscuity of Vibrio dual lipase/transferase.
Nat Commun, 14:4795-4795, 2023

PubMed Abstract: 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.

PubMed: 37558668
DOI: 10.1038/s41467-023-40455-y

Experimental method

X-RAY DIFFRACTION (1.931 Å)