4yz7

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(Difference between revisions)

Revision as of 13:24, 10 May 2017

Crystal structure of Piratoxin I (PrTX-I) complexed to aristolochic acid

Structural highlights

4yz7 is a 2 chain structure with sequence from Bothrops pirajai. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

One of the main challenges in toxicology today is to develop therapeutic alternatives for the treatment of snake venom injuries that are not efficiently neutralized by conventional serum therapy. Venom phospholipases A2 (PLA2s) and PLA2-like proteins play a fundamental role in skeletal muscle necrosis, which can result in permanent sequelae and disability. This leads to economic and social problems, especially in developing countries. In this work, we performed structural and functional studies with Piratoxin-I, a Lys49-PLA2 from Bothropspirajai venom, complexed with two compounds present in several plants used in folk medicine against snakebites. These ligands partially neutralized the myotoxic activity of PrTX-I towards binding on the two independent sites of interaction between Lys49-PLA2 and muscle membrane. Our results corroborate the previously proposed mechanism of action of PLA2s-like and provide insights for the design of structure-based inhibitors that could prevent the permanent injuries caused by these proteins in snakebite victims.

Structural Basis for the Inhibition of a Phospholipase A2-Like Toxin by Caffeic and Aristolochic Acids.,Fernandes CA, Cardoso FF, Cavalcante WG, Soares AM, Dal-Pai M, Gallacci M, Fontes MR PLoS One. 2015 Jul 20;10(7):e0133370. doi: 10.1371/journal.pone.0133370., eCollection 2015. PMID:26192963^[3]

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

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
↑ Fernandes CA, Cardoso FF, Cavalcante WG, Soares AM, Dal-Pai M, Gallacci M, Fontes MR. Structural Basis for the Inhibition of a Phospholipase A2-Like Toxin by Caffeic and Aristolochic Acids. PLoS One. 2015 Jul 20;10(7):e0133370. doi: 10.1371/journal.pone.0133370., eCollection 2015. PMID:26192963 doi:http://dx.doi.org/10.1371/journal.pone.0133370

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4yz7"

@@ Line 1: / Line 1: @@
 ==Crystal structure of Piratoxin I (PrTX-I) complexed to aristolochic acid==
 <StructureSection load='4yz7' size='340' side='right' caption='[[4yz7]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[4yz7]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bothrops_pirajai Bothrops pirajai]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YZ7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YZ7 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9AR:9-HYDROXY+ARISTOLOCHIC+ACID'>9AR</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></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=4yz7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yz7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4yz7 RCSB], [http://www.ebi.ac.uk/pdbsum/4yz7 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=4yz7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yz7 OCA], [http://pdbe.org/4yz7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yz7 RCSB], [http://www.ebi.ac.uk/pdbsum/4yz7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yz7 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4yz7" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4yz7

From Proteopedia

Revision as of 13:24, 10 May 2017

Crystal structure of Piratoxin I (PrTX-I) complexed to aristolochic acid

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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