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| | <StructureSection load='3h1x' size='340' side='right'caption='[[3h1x]], [[Resolution|resolution]] 1.40Å' scene=''> | | <StructureSection load='3h1x' size='340' side='right'caption='[[3h1x]], [[Resolution|resolution]] 1.40Å' scene=''> |
| | == Structural highlights == | | == 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://proteopedia.org/fgij/fg.htm?mol=3H1X FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3h1x]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Daboia_russelii_russelii Daboia russelii russelii]. 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 [https://proteopedia.org/fgij/fg.htm?mol=3H1X FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IMN:INDOMETHACIN'>IMN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1fb2|1fb2]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IMN:INDOMETHACIN'>IMN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=3h1x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3h1x OCA], [https://pdbe.org/3h1x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3h1x RCSB], [https://www.ebi.ac.uk/pdbsum/3h1x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3h1x ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/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> | | </table> |
| | == Function == | | == Function == |
| - | [[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> | + | [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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Daboia russellii russellii]] | + | [[Category: Daboia russelii russelii]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Kaur, P]] | + | [[Category: Kaur P]] |
| - | [[Category: Kumar, R Prem]] | + | [[Category: Prem Kumar R]] |
| - | [[Category: Sharma, S]] | + | [[Category: Sharma S]] |
| - | [[Category: Singh, N]] | + | [[Category: Singh N]] |
| - | [[Category: Singh, T P]] | + | [[Category: Singh TP]] |
| - | [[Category: Anti-coagulant]]
| + | |
| - | [[Category: Anti-inflammatory]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Indomethacin]]
| + | |
| - | [[Category: Pla2]]
| + | |
| Structural highlights
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.
See Also
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
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