1oxl
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(New page: 200px<br /><applet load="1oxl" size="450" color="white" frame="true" align="right" spinBox="true" caption="1oxl, resolution 1.80Å" /> '''INHIBITION OF PHOSPH...)
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Revision as of 21:09, 20 November 2007
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INHIBITION OF PHOSPHOLIPASE A2 (PLA2) BY (2-CARBAMOYLMETHYL-5-PROPYL-OCTAHYDRO-INDOL-7-YL)-ACETIC ACID (INDOLE): CRYSTAL STRUCTURE OF THE COMPLEX FORMED BETWEEN PLA2 FROM RUSSELL'S VIPER AND INDOLE AT 1.8 RESOLUTION
Overview
Phospholipase A2 (PLA2) enzymes from snake venoms are approximately 14 kDa, secretory proteins and catalyze the release of arachidonic acid which is, the precursor of proinflammatory mediators such as prostaglandins, leukotrienes, thromboxanes and platelet-activating factors. The structure, of the PLA2 enzyme purified from the venom of Daboia russelli pulchella, was determined using molecular replacement method and refined to an R, value of 18.3% for all the reflections to 1.8 A resolution. The structure, contains two crystallographically independent molecules A and B which form, an asymmetric homodimer. The Ca2+ ion was not detected in the present, structure, however, a characteristic non-protein high quality electron, density was observed at the substrate-binding site of molecule A which, allowed a clear interpretation of a natural ligand identified as a, derivative of indole, 2-carbamoylmethyl-5-propyl-octahydro-indol-7-yl)-acetic acid. The, corresponding substrate-binding site in molecule B was empty. The ligand, present in molecule A is involved in extensive interactions with the, protein atoms including important catalytic residues such as Asp-49 and, His-48. The results also show that the indole derivatives act as potent, inhibitors of secretory group II PLA2 enzymes that can be further modified, to be used as potential therapeutic agents.
About this Structure
1OXL is a Single protein structure of sequence from Daboia russellii russellii with CO3, SO4 and IDA as ligands. Active as Phospholipase A(2), with EC number 3.1.1.4 Full crystallographic information is available from OCA.
Reference
Crystal structure of the complex of the secretory phospholipase A2 from Daboia russelli pulchella with an endogenic indole derivative, 2-carbamoylmethyl-5-propyl-octahydro-indol-7-yl-acetic acid at 1.8 A resolution., Balasubramanya R, Chandra V, Kaur P, Singh TP, Biochim Biophys Acta. 2005 Sep 25;1752(2):177-85. PMID:16122995
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