4qgd: Difference between revisions
New page: '''Unreleased structure''' The entry 4qgd is ON HOLD Authors: Shukla, P.K. , Sinha, M. , Kaur, P. , Sharma, S., Singh, T.P. Description: Crystal Structure of the Complex of Phospholipa... |
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==Crystal Structure of the Complex of Phospholipase A2 with Gramine derivative at 1.80 A Resolution== | |||
<StructureSection load='4qgd' size='340' side='right'caption='[[4qgd]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4qgd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Daboia_russelii_pulchella Daboia russelii pulchella]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QGD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QGD FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PZZ:3-{3-[(DIMETHYLAMINO)METHYL]-1H-INDOL-7-YL}PROPAN-1-OL'>PZZ</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4qgd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qgd OCA], [https://pdbe.org/4qgd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qgd RCSB], [https://www.ebi.ac.uk/pdbsum/4qgd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qgd ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PA2B8_DABRR 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.<ref>PMID:18062812</ref> <ref>PMID:2115497</ref> <ref>PMID:8835338</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Phospholipase A2 (PLA2) catalyzes the hydrolysis of phospholipids into arachidonic acid and lysophospholipids. Arachidonic acid is used as a substrate in the next step of the multistep pathway leading to the production of eicosanoids. The eicosanoids, in extremely low concentrations, are required in a number of physiological processes. However, the increase in their concentrations above the essential physiological requirements leads to various inflammatory conditions. In order to prevent the unwanted rise in the concentrations of eicosanoids, the actions of PLA2 and other enzymes of the pathway need to be blocked. We report here the structures of five complexes of group IIA PLA2 from Daboia russelli pulchella with tightly binding inhibitors, (i) p-coumaric acid, (ii) resveratrol, (iii) spermidine, (iv) corticosterone and (v) gramine derivative. The binding studies using fluorescence spectroscopy and surface plasmon resonance techniques for the interactions of PLA2 with the above five compounds showed high binding affinities with values of dissociation constants (KD) ranging from 3.7x10-8M to 2.1x10-9M. The structure determinations of the complexes of PLA2 with the above five compounds showed that all the compounds bound to PLA2 in the substrate binding cleft. The protein residues that contributed to the interactions with these compounds included Leu2, Leu3, Phe5, Gly6, Ile9, Ala18, Ile19, Trp22, Ser23, Cys29, Gly30, Cys45, His48, Asp49 and Phe106. The positions of side chains of several residues including Leu2, Leu3, Ile19, Trp31, Lys69, Ser70 and Arg72 got significantly shifted while the positions of active site residues, His48, Asp49, Tyr52 and Asp99 were unperturbed. | |||
Structures and binding studies of the complexes of phospholipase A2 with five inhibitors.,Shukla PK, Gautam L, Sinha M, Kaur P, Sharma S, Singh TP Biochim Biophys Acta. 2014 Dec 23;1854(4):269-277. doi:, 10.1016/j.bbapap.2014.12.017. PMID:25541253<ref>PMID:25541253</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4qgd" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Phospholipase A2 3D structures|Phospholipase A2 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Daboia russelii pulchella]] | |||
[[Category: Large Structures]] | |||
[[Category: Kaur P]] | |||
[[Category: Sharma S]] | |||
[[Category: Shukla PK]] | |||
[[Category: Singh TP]] | |||
[[Category: Sinha M]] | |||