Structural highlights
Function[PA24D_HUMAN] Calcium-dependent phospholipase A2 that selectively hydrolyzes glycerophospholipids in the sn-2 position. Not arachidonic acid-specific but has linoleic acid-specific activity. May play a role in inflammation in psoriatic lesions.[1] Publication Abstract from PubMedCytosolic phospholipases A2 (cPLA2s) consist of a family of calcium-sensitive enzymes that function to generate lipid second messengers through hydrolysis of membrane-associated glycerophospholipids. The GIVD cPLA2 (cPLA2delta) is a potential drug target for developing a selective therapeutic agent for the treatment of psoriasis. Here, we present two X-ray structures of human cPLA2delta, capturing an apo state, and in complex with a substrate-like inhibitor. Comparison of the apo and inhibitor-bound structures reveals conformational changes in a flexible cap that allows the substrate to access the relatively buried active site, providing new insight into the mechanism for substrate recognition. The cPLA2delta structure reveals an unexpected second C2 domain that was previously unrecognized from sequence alignments, placing cPLA2delta into the class of membrane-associated proteins that contain a tandem pair of C2 domains. Furthermore, our structures elucidate novel inter-domain interactions and define three potential calcium-binding sites that are likely important for regulation and activation of enzymatic activity. These findings provide novel insights into the molecular mechanisms governing cPLA2's function in signal transduction. Structure of Human GIVD Cytosolic Phospholipase A2 Reveals Insights into Substrate Recognition.,Wang H, Klein MG, Snell G, Lane W, Zou H, Levin I, Li K, Sang BC J Mol Biol. 2016 Jul 3;428(13):2769-79. doi: 10.1016/j.jmb.2016.05.012. Epub 2016, May 21. PMID:27220631[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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