3h1x

From Proteopedia

(Difference between revisions)

Revision as of 08:01, 5 August 2016

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

Structural highlights

3h1x is a 1 chain structure with sequence from Dabrr. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1fb2
Activity:	Phospholipase A(2), with EC number 3.1.1.4
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.^[1] ^[2] ^[3]

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Faure G, Gowda VT, Maroun RC. Characterization of a human coagulation factor Xa-binding site on Viperidae snake venom phospholipases A2 by affinity binding studies and molecular bioinformatics. BMC Struct Biol. 2007 Dec 6;7:82. PMID:18062812 doi:http://dx.doi.org/10.1186/1472-6807-7-82
↑ Kasturi S, Rudrammaji LM, Gowda TV. Antibodies to a phospholipase A2 from Vipera russelli selectively neutralize venom neurotoxicity. Immunology. 1990 Jun;70(2):175-80. PMID:2115497
↑ Tsai IH, Lu PJ, Su JC. Two types of Russell's viper revealed by variation in phospholipases A2 from venom of the subspecies. Toxicon. 1996 Jan;34(1):99-109. PMID:8835338
↑ Singh N, Kumar RP, Kumar S, Sharma S, Mir R, Kaur P, Srinivasan A, Singh TP. 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. J Mol Recognit. 2009 May 21. PMID:19462410 doi:10.1002/jmr.960

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3h1x"

@@ Line 1: / Line 1: @@
 ==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==
 <StructureSection load='3h1x' size='340' side='right' caption='[[3h1x]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3h1x]] is a 1 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=3H1X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3H1X FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3h1x]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Dabrr Dabrr]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3H1X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3H1X FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IMN:INDOMETHACIN'>IMN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1fb2|1fb2]]</td></tr>
 <tr id='activity'><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 id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3h1x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3h1x OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3h1x RCSB], [http://www.ebi.ac.uk/pdbsum/3h1x PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3h1x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3h1x OCA], [http://pdbe.org/3h1x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3h1x RCSB], [http://www.ebi.ac.uk/pdbsum/3h1x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3h1x ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/PA28_DABRR PA28_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:8835338</ref> <ref>PMID:2115497</ref> <ref>PMID:18062812</ref>
+[[http://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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 18: / Line 19: @@
     <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].
+</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/main_output.php?pdb_ID=3h1x ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 28: / Line 29: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3h1x" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 35: / Line 37: @@
 __TOC__
 </StructureSection>
-[[Category: Daboia russellii russellii]]
+[[Category: Dabrr]]
 [[Category: Kaur, P]]
 [[Category: Kumar, R Prem]]

3h1x

From Proteopedia

Revision as of 08:01, 5 August 2016

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

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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