Molecular insights on PS-PLA1 lipase activity of human ABHD16B

Raja, Narayanasamy and Ram, Rajasekharan and Dandamudi, Usharani (2023) Molecular insights on PS-PLA1 lipase activity of human ABHD16B. Biophysical Chemistry, 296. pp. 1-11.

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Abstract

The human alpha beta hydrolase domain (ABHD) proteins are ubiquitous and regulate the cellular lipids’ anabolic and catabolic processes. The structural aspects for specific biochemical function of many ABHD proteins related to physiological disorders and its link to pathological conditions remain unknown. Here putative human ABHD16B protein was overexpressed in Saccharomyces cerevisiae for its biological activity. In-vitro enzymatic assay of the recombinant ABHD16B protein with fluorescently tagged glycerophospholipids revealed that the PLA1 activity is observed with phosphatidylserine (PS). In addition, it efficiently hydrolyzed monoacylglycerol over triacylglycerols. Further, molecular dynamic simulations and per residue binding free energy decomposition analysis revealed that the origin of PS-specific PLA1 activity of ABHD16B is due to the electrostatic interaction of the PS head group with K8, R319, and E178, which led to having the hydrogen bond interaction of sn-1 acyl chain ester to the catalytic site residues. Site-directed mutagenesis of the 245GXSXG249 motif of ABHD16B reduced the maximal lipase activity of PS and MAG. In summary, these results revealed that ABHD16B plays a vital role in PS selectivity that in turn, controls the specific subcellular pools of 2-LPS metabolism in the tissues at low pH.

Item Type:	Article
Uncontrolled Keywords:	Lipase, PS-PLA1, Lipase motif, Site-directed mutagenesis, Molecular simulation
Subjects:	500 Natural Sciences and Mathematics > 07 Life Sciences > 03 Biochemistry & Molecular Biology > 13 Molecular Biochemistry 600 Technology > 08 Food technology > 16 Nutritive value > 05 Enzymes
Divisions:	Food Safety Analytical Quality Control Lab
Depositing User:	Somashekar K S
Date Deposited:	05 Mar 2025 10:33
Last Modified:	05 Mar 2025 10:33
URI:	http://ir.cftri.res.in/id/eprint/19182

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