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| | <StructureSection load='1q7a' size='340' side='right'caption='[[1q7a]], [[Resolution|resolution]] 1.60Å' scene=''> | | <StructureSection load='1q7a' size='340' side='right'caption='[[1q7a]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1q7a]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Daboia_russellii_pulchella Daboia russellii pulchella]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q7A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Q7A FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1q7a]] 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=1Q7A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Q7A FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MOH:METHANOL'>MOH</scene>, <scene name='pdbligand=OPB:4-BUTYL-1-(4-HYDROXYPHENYL)-2-PHENYLPYRAZOLIDINE-3,5-DIONE'>OPB</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]] 1.6Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1cl5|1cl5]], [[1oyf|1oyf]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MOH:METHANOL'>MOH</scene>, <scene name='pdbligand=OPB:4-BUTYL-1-(4-HYDROXYPHENYL)-2-PHENYLPYRAZOLIDINE-3,5-DIONE'>OPB</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'>[https://en.wikipedia.org/wiki/Phospholipase_A(2) Phospholipase A(2)], with EC number [https://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=1q7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q7a OCA], [https://pdbe.org/1q7a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1q7a RCSB], [https://www.ebi.ac.uk/pdbsum/1q7a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1q7a ProSAT]</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=1q7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q7a OCA], [https://pdbe.org/1q7a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1q7a RCSB], [https://www.ebi.ac.uk/pdbsum/1q7a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1q7a ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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>
| + | [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 pulchella]] | + | [[Category: Daboia russelii pulchella]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Jabeen, T]] | + | [[Category: Jabeen T]] |
| - | [[Category: Sharma, S]] | + | [[Category: Sharma S]] |
| - | [[Category: Singh, N]] | + | [[Category: Singh N]] |
| - | [[Category: Singh, T P]] | + | [[Category: Singh TP]] |
| - | [[Category: Antiinflammatory compound]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Phospholipase a2]]
| + | |
| - | [[Category: Venom]]
| + | |
| 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
Phospholipase A(2) (PLA(2); EC 3.1.1.4) is a key enzyme involved in the production of proinflammatory mediators known as eicosanoids. The binding of the substrate to PLA(2) occurs through a well-formed hydrophobic channel. To determine the viability of PLA(2) as a target molecule for the structure-based drug design against inflammation, arthritis, and rheumatism, the crystal structure of the complex of PLA(2) with a known anti-inflammatory compound oxyphenbutazone (OPB), which has been determined at 1.6 A resolution. The structure has been refined to an R factor of 0.209. The structure contains 1 molecule each of PLA(2) and OPB with 2 sulfate ions and 111 water molecules. The binding studies using surface plasmon resonance show that OPB binds to PLA(2) with a dissociation constant of 6.4 x 10(-8) M. The structure determination has revealed the presence of an OPB molecule at the binding site of PLA(2). It fits well in the binding region, thus displaying a high level of complementarity. The structure also indicates that OPB works as a competitive inhibitor. A large number of hydrophobic interactions between the enzyme and the OPB molecule have been observed. The hydrophobic interactions involving residues Tyr(52) and Lys(69) with OPB are particularly noteworthy. Other residues of the hydrophobic channel such as Leu(3), Phe(5), Met(8), Ile(9), and Ala(18) are also interacting extensively with the inhibitor. The crystal structure clearly reveals that the binding of OPB to PLA(2) is specific in nature and possibly suggests that the basis of its anti-inflammatory effects may be due to its binding to PLA(2) as well.
Phospholipase A2 as a target protein for nonsteroidal anti-inflammatory drugs (NSAIDS): crystal structure of the complex formed between phospholipase A2 and oxyphenbutazone at 1.6 A resolution.,Singh N, Jabeen T, Somvanshi RK, Sharma S, Dey S, Singh TP Biochemistry. 2004 Nov 23;43(46):14577-83. PMID:15544328[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, Jabeen T, Somvanshi RK, Sharma S, Dey S, Singh TP. Phospholipase A2 as a target protein for nonsteroidal anti-inflammatory drugs (NSAIDS): crystal structure of the complex formed between phospholipase A2 and oxyphenbutazone at 1.6 A resolution. Biochemistry. 2004 Nov 23;43(46):14577-83. PMID:15544328 doi:10.1021/bi0483561
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