5izr

Human GIVD cytosolic phospholipase A2 in complex with Methyl gamma-Linolenyl Fluorophosphonate inhibitor and Terbium Chloride

spinqualitylabelsall models 5izr, resolution 3.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5izr is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.25Å Ligands: 7FA, TB Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. Publication Abstract from PubMed Cytosolic 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phospholipase A2 3D structures

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