1oxl: Difference between revisions
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[[Image: | ==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== | ||
<StructureSection load='1oxl' size='340' side='right' caption='[[1oxl]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1oxl]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Daboia_russellii_russellii Daboia russellii russellii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OXL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1OXL FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=IDA:(2-CARBAMOYLMETHYL-5-PROPYL-OCTAHYDRO-INDOL-7-YL)ACETIC+ACID'>IDA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1cl5|1cl5]], [[1fb2|1fb2]]</td></tr> | |||
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phospholipase_A(2) Phospholipase A(2)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.4 3.1.1.4] </span></td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1oxl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oxl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1oxl RCSB], [http://www.ebi.ac.uk/pdbsum/1oxl PDBsum]</span></td></tr> | |||
<table> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ox/1oxl_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
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<ref>PMID:16122995</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Phospholipase A2|Phospholipase A2]] | *[[Phospholipase A2|Phospholipase A2]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Daboia russellii russellii]] | [[Category: Daboia russellii russellii]] | ||
[[Category: Balasubramanya, R.]] | [[Category: Balasubramanya, R.]] | ||
Revision as of 23:00, 28 September 2014
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 RESOLUTIONINHIBITION 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
Structural highlights
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 PubMedPhospholipase 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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