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| | <StructureSection load='4yv5' size='340' side='right'caption='[[4yv5]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='4yv5' size='340' side='right'caption='[[4yv5]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4yv5]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bothrops_moojeni Bothrops moojeni]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YV5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YV5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4yv5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bothrops_moojeni Bothrops moojeni]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YV5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YV5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=SVR:8,8-[CARBONYLBIS[IMINO-3,1-PHENYLENECARBONYLIMINO(4-METHYL-3,1-PHENYLENE)CARBONYLIMINO]]BIS-1,3,5-NAPHTHALENETRISULFONIC+ACID'>SVR</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=SVR:8,8-[CARBONYLBIS[IMINO-3,1-PHENYLENECARBONYLIMINO(4-METHYL-3,1-PHENYLENE)CARBONYLIMINO]]BIS-1,3,5-NAPHTHALENETRISULFONIC+ACID'>SVR</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4kf3|4kf3]]</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=4yv5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yv5 OCA], [https://pdbe.org/4yv5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yv5 RCSB], [https://www.ebi.ac.uk/pdbsum/4yv5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yv5 ProSAT]</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=4yv5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yv5 OCA], [http://pdbe.org/4yv5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yv5 RCSB], [http://www.ebi.ac.uk/pdbsum/4yv5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yv5 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PA2H2_BOTMO PA2H2_BOTMO]] Snake venom phospholipase A2 homolog that lack enzymatic activity. Displays myotoxin and edema-inducing activities. | + | [https://www.uniprot.org/uniprot/PA2H2_BOTMO PA2H2_BOTMO] Snake venom phospholipase A2 homolog that lack enzymatic activity. Displays myotoxin and edema-inducing activities. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4yv5" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4yv5" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Phospholipase A2 homolog|Phospholipase A2 homolog]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | [[Category: Bothrops moojeni]] | | [[Category: Bothrops moojeni]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Fontes, M R.M]] | + | [[Category: Fontes MRM]] |
| - | [[Category: Salvador, G H.M]] | + | [[Category: Salvador GHM]] |
| - | [[Category: Lys49-pla2]]
| + | |
| - | [[Category: Myotoxin ii]]
| + | |
| - | [[Category: Suramin]]
| + | |
| - | [[Category: Toxin]]
| + | |
| Structural highlights
Function
PA2H2_BOTMO Snake venom phospholipase A2 homolog that lack enzymatic activity. Displays myotoxin and edema-inducing activities.
Publication Abstract from PubMed
Local myonecrosis resulting from snakebite envenomation is not efficiently neutralized by regular antivenom administration. This limitation is considered to be a significant health problem by the World Health Organization. Phospholipase A2-like (PLA2-like) proteins are among the most important proteins related to the muscle damage resulting from several snake venoms. However, despite their conserved tertiary structure compared with PLA2s, their biological mechanism remains incompletely understood. Different oligomeric conformations and binding sites have been identified or proposed, leading to contradictory data in the literature. In the last few years, a comprehensive hypothesis has been proposed based on fatty-acid binding, allosteric changes and the presence of two different interaction sites. In the present study, a combination of techniques were used to fully understand the structural-functional characteristics of the interaction between suramin and MjTX-II (a PLA2-like toxin). In vitro neuromuscular studies were performed to characterize the biological effects of the protein-ligand interaction and demonstrated that suramin neutralizes the myotoxic activity of MjTX-II. The high-resolution structure of the complex identified the toxin-ligand interaction sites. Calorimetric assays showed two different binding events between the protein and the inhibitor. It is demonstrated for the first time that the inhibitor binds to the surface of the toxin, obstructing the sites involved in membrane docking and disruption according to the proposed myotoxic mechanism. Furthermore, higher-order oligomeric formation by interaction with interfacial suramins was observed, which may also aid the inhibitory process. These results further substantiate the current myotoxic mechanism and shed light on the search for efficient inhibitors of the local myonecrosis phenomenon.
Structural and functional evidence for membrane docking and disruption sites on phospholipase A2-like proteins revealed by complexation with the inhibitor suramin.,Salvador GH, Dreyer TR, Cavalcante WL, Matioli FF, Dos Santos JI, Velazquez-Campoy A, Gallacci M, Fontes MR Acta Crystallogr D Biol Crystallogr. 2015 Oct;71(Pt 10):2066-78. doi:, 10.1107/S1399004715014443. Epub 2015 Sep 26. PMID:26457430[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Salvador GH, Dreyer TR, Cavalcante WL, Matioli FF, Dos Santos JI, Velazquez-Campoy A, Gallacci M, Fontes MR. Structural and functional evidence for membrane docking and disruption sites on phospholipase A2-like proteins revealed by complexation with the inhibitor suramin. Acta Crystallogr D Biol Crystallogr. 2015 Oct;71(Pt 10):2066-78. doi:, 10.1107/S1399004715014443. Epub 2015 Sep 26. PMID:26457430 doi:http://dx.doi.org/10.1107/S1399004715014443
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