3h1x

Simultaneous inhibition of anti-coagulation and inflammation: Crystal structure of phospholipase A2 complexed with indomethacin at 1.4 A resolution reveals the presence of the new common ligand binding site

spinqualitylabelsall models 3h1x, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3h1x is a 1 chain structure with sequence from Daboia russelii russelii. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.4Å Ligands: IMN, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PA2B8_DABRR Snake venom phospholipase A2 (PLA2) that shows weak neurotoxicity and medium anticoagulant effects by binding to factor Xa (F10) and inhibiting the prothrombinase activity (IC(50) is 130 nM) (PubMed:18062812). It also damages vital organs such as lung, liver and kidney, displays edema-inducing activities when injected into the foot pads of mice and induces necrosis of muscle cells when injected into the thigh muscle. Has a low enzymatic activity. PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed A novel ligand-binding site with functional implications has been identified in phospholipase A(2) (PLA(2)). The binding of non-steroidal anti-inflammatory agent indomethacin at this site blocks both catalytic and anti-coagulant actions of PLA(2). A group IIA PLA(2) has been isolated from Daboia russelli pulchella (Russell's viper) which is enzymatically active as well as induces a strong anti-coagulant action. The binding studies have shown that indomethacin reduces the effects of both anti-coagulant and pro-inflammatory actions of PLA(2). A group IIA PLA(2) was co-crystallized with indomethacin and the structure of the complex has been determined at 1.4 A resolution. The structure determination has revealed the presence of an indomethacin molecule in the structure of PLA(2) at a site which is distinct from the conventional substrate-binding site. One of the carboxylic group oxygen atoms of indomethacin interacts with Asp 49 and His 48 through the catalytically important water molecule OW 18 while the second carboxylic oxygen atom forms an ionic interaction with the side chain of Lys 69. It is well known that the residues, His 48 and Asp 49 are essential for catalysis while Lys 69 is a part of the anti-coagulant loop (residues, 54-77). Indomethacin binds in such a manner that it blocks the access to both, it works as a dual inhibitor for catalytic and anti-coagulant actions of PLA(2). This new binding site in PLA(2) has been observed for the first time and indomethacin is the first compound that has been shown to bind at this novel site resulting in the prevention of anti-coagulation and inflammation. Copyright (c) 2009 John Wiley & Sons, Ltd. Simultaneous inhibition of anti-coagulation and inflammation: crystal structure of phospholipase A(2) complexed with indomethacin at 1.4 A resolution reveals the presence of the new common ligand-binding site.,Singh N, Kumar RP, Kumar S, Sharma S, Mir R, Kaur P, Srinivasan A, Singh TP J Mol Recognit. 2009 May 21. PMID:19462410 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phospholipase A2 3D structures

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