Structural and enzymatic analysis of a dimeric cholylglycine hydrolase like acylase active on N-acyl homoserine lactones

The prevalence of substrate cross-reactivity between AHL acylases and β-lactam acylases provides a glimpse of probable links between quorum sensing and antibiotic resistance in bacteria. Both these enzyme classes belong to the N-terminal nucleophile (Ntn)-hydrolase superfamily. Penicillin V acylases...

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Published in:	Biochimie Vol. 177; pp. 108 - 116
Main Authors:	Philem, Pushparani D., Yadav, Yashpal, Vellore Sunder, Avinash, Ghosh, Deepanjan, Prabhune, Asmita, Ramasamy, Sureshkumar
Format:	Journal Article
Language:	English
Published:	Elsevier B.V 01-10-2020
Subjects:	AHL acylase Cholyolglycine hydrolase Homodimer Ntn-fold Shewanella loihica-PV4 Cholyolglycine hydrolase Homodimer Ntn-fold Shewanella loihica-PV4 AHL acylase
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Summary:	The prevalence of substrate cross-reactivity between AHL acylases and β-lactam acylases provides a glimpse of probable links between quorum sensing and antibiotic resistance in bacteria. Both these enzyme classes belong to the N-terminal nucleophile (Ntn)-hydrolase superfamily. Penicillin V acylases alongside bile salt hydrolases constitute the cholylglycine hydrolase (CGH) group of the Ntn-hydrolase superfamily. Here we report the ability of two acylases, Slac1 and Slac2, from the marine bacterium Shewanella loihica-PV4 to hydrolyze AHLs. Three-dimensional structure of Slac1reveals the conservation of the Ntn hydrolase fold and CGH active site, making it a unique CGH exclusively active on AHLs. Slac1homologs phylogenetically cluster separate from reported CGHs and AHL acylases, thereby representing a functionally distinct sub-class of CGH that might have evolved as an adaptation to the marine environment. We hypothesize that Slac1 could provide the structural framework for understanding this subclass, and further our understanding of the evolutionary link between AHL acylases and β-lactam acylases. •Choloylglycine hydrolase homologs Slac1 and Slac2 from Shewanella loihica exhibit AHL acylase activity while inactive as CGHs.•Crystal structures of homodimeric Slac1 alone and in complex with the hydrolysed product.•Subtrate specificity explained in terms of changes in residues and loops in binding pocket.•Slac1 and homologs might represent a new sub-class of AHL acylases with CGH structural framework.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0300-9084 1638-6183
DOI:	10.1016/j.biochi.2020.07.017