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| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[3qnl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bothrops_pirajai Bothrops pirajai]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QNL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QNL FirstGlance]. <br> | | <table><tr><td colspan='2'>[[3qnl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bothrops_pirajai Bothrops pirajai]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QNL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QNL FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=P33:3,6,9,12,15,18-HEXAOXAICOSANE-1,20-DIOL'>P33</scene>, <scene name='pdbligand=ROA:(2R)-3-(3,4-DIHYDROXYPHENYL)-2-{[(2E)-3-(3,4-DIHYDROXYPHENYL)PROP-2-ENOYL]OXY}PROPANOIC+ACID'>ROA</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]] 1.77Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2q2j|2q2j]], [[3cyl|3cyl]], [[1xxs|1xxs]], [[1y4l|1y4l]], [[2ok9|2ok9]], [[1qll|1qll]], [[1pa0|1pa0]], [[3i3h|3i3h]], [[3cxi|3cxi]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=P33:3,6,9,12,15,18-HEXAOXAICOSANE-1,20-DIOL'>P33</scene>, <scene name='pdbligand=ROA:(2R)-3-(3,4-DIHYDROXYPHENYL)-2-{[(2E)-3-(3,4-DIHYDROXYPHENYL)PROP-2-ENOYL]OXY}PROPANOIC+ACID'>ROA</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=3qnl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qnl OCA], [https://pdbe.org/3qnl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qnl RCSB], [https://www.ebi.ac.uk/pdbsum/3qnl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qnl 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=3qnl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qnl OCA], [https://pdbe.org/3qnl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qnl RCSB], [https://www.ebi.ac.uk/pdbsum/3qnl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qnl ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/PA2H1_BOTPI PA2H1_BOTPI]] Snake venom phospholipase A2 (PLA2) homolog that lacks enzymatic activity, but displays myotoxin and edema-inducing activities in vivo. In vitro neuromuscular activities have also been observed, but they are not found in vivo and can be explained by the destabilization of the muscle membrane by the toxin. The myotoxic activity is inhibited by rosmarinic acid (RA).<ref>PMID:7660366</ref> <ref>PMID:22205953</ref>
| + | [https://www.uniprot.org/uniprot/PA2H1_BOTPI PA2H1_BOTPI] Snake venom phospholipase A2 (PLA2) homolog that lacks enzymatic activity, but displays myotoxin and edema-inducing activities in vivo. In vitro neuromuscular activities have also been observed, but they are not found in vivo and can be explained by the destabilization of the muscle membrane by the toxin. The myotoxic activity is inhibited by rosmarinic acid (RA).<ref>PMID:7660366</ref> <ref>PMID:22205953</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | [[Category: Bothrops pirajai]] | | [[Category: Bothrops pirajai]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Fontes, M R.M]] | + | [[Category: Fontes MRM]] |
| - | [[Category: Santos, J I.dos]] | + | [[Category: Dos Santos JI]] |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
PA2H1_BOTPI Snake venom phospholipase A2 (PLA2) homolog that lacks enzymatic activity, but displays myotoxin and edema-inducing activities in vivo. In vitro neuromuscular activities have also been observed, but they are not found in vivo and can be explained by the destabilization of the muscle membrane by the toxin. The myotoxic activity is inhibited by rosmarinic acid (RA).[1] [2]
Publication Abstract from PubMed
Snakebite envenoming is an important public health problem in many tropical and subtropical countries, and is considered a neglected tropical disease by the World Health Organization. Most severe cases are inflicted by species of the families Elapidae and Viperidae, and lead to a number of systemic and local effects in the victim. One of the main problems regarding viperidic accidents is prominent local tissue damage whose pathogenesis is complex and involves the combined actions of a variety of venom components. Phospholipases A (PLAs) are the most abundant muscle-damaging components of these venoms. Herein, we report functional and structural studies of PrTX-I, a Lys49-PLA from Bothops pirajai snake venom, and the influence of rosmarinic acid (RA) upon this toxin's activities. RA is a known active component of some plant extracts and has been reported as presenting anti-myotoxic properties related to bothopic envenomation. The myotoxic activity of Lys49-PLAs is well established in the literature and although no in vivo neurotoxicity has been observed among these toxins, in vitro neuromuscular blockade has been reported for some of these proteins. Our in vitro studies show that RA drastically reduces both the muscle damage and the neuromuscular blockade exerted by PrTX-I on mice neuromuscular preparations (by approximately 80% and approximately 90%, respectively). These results support the hypothesis that the two effects are closely related and lead us to suggest that they are consequences of the muscle membrane-destabilizing activity of the Lys49-PLA. Although the C-terminal region of these proteins has been reported to comprise the myotoxic site, we demonstrate by X-ray crystallographic studies that RA interacts with PrTX-I in a different region. Consequently, a new mode of Lys49-PLA inhibition is proposed. Comparison of our results with others in the literature suggests possible new ways to inhibit bothropic snake venom myotoxins and improve serum therapy.
Structural and functional studies of a bothropic myotoxin complexed to rosmarinic acid: new insights into Lys49-PLA inhibition.,Dos Santos JI, Cardoso FF, Soares AM, Dal Pai Silva M, Gallacci M, Fontes MR PLoS One. 2011;6(12):e28521. Epub 2011 Dec 21. PMID:22205953[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mancuso LC, Correa MM, Vieira CA, Cunha OA, Lachat JJ, de Araujo HS, Ownby CL, Giglio JR. Fractionation of Bothrops pirajai snake venom: isolation and characterization of piratoxin-I, a new myotoxic protein. Toxicon. 1995 May;33(5):615-26. PMID:7660366
- ↑ Dos Santos JI, Cardoso FF, Soares AM, Dal Pai Silva M, Gallacci M, Fontes MR. Structural and functional studies of a bothropic myotoxin complexed to rosmarinic acid: new insights into Lys49-PLA inhibition. PLoS One. 2011;6(12):e28521. Epub 2011 Dec 21. PMID:22205953 doi:10.1371/journal.pone.0028521
- ↑ Dos Santos JI, Cardoso FF, Soares AM, Dal Pai Silva M, Gallacci M, Fontes MR. Structural and functional studies of a bothropic myotoxin complexed to rosmarinic acid: new insights into Lys49-PLA inhibition. PLoS One. 2011;6(12):e28521. Epub 2011 Dec 21. PMID:22205953 doi:10.1371/journal.pone.0028521
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