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| | <StructureSection load='2q2j' size='340' side='right'caption='[[2q2j]], [[Resolution|resolution]] 1.65Å' scene=''> | | <StructureSection load='2q2j' size='340' side='right'caption='[[2q2j]], [[Resolution|resolution]] 1.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2q2j]] 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=2Q2J OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2Q2J FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2q2j]] 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=2Q2J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q2J FirstGlance]. <br> |
| | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr> | | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1pa0|1pa0]], [[1pc9|1pc9]], [[1os4|1os4]], [[1xxs|1xxs]], [[1y4l|1y4l]], [[1qll|1qll]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1pa0|1pa0]], [[1pc9|1pc9]], [[1os4|1os4]], [[1xxs|1xxs]], [[1y4l|1y4l]], [[1qll|1qll]]</div></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=2q2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q2j OCA], [http://pdbe.org/2q2j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2q2j RCSB], [http://www.ebi.ac.uk/pdbsum/2q2j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2q2j 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=2q2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q2j OCA], [https://pdbe.org/2q2j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q2j RCSB], [https://www.ebi.ac.uk/pdbsum/2q2j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q2j ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| 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]
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
Phospholipases A(2) (PLA(2)s) are membrane-associated enzymes that hydrolyze phospholipids at the sn-2 position, releasing lysophospholipids and free fatty acids. Phospholipase A(2) homologues (Lys49-PLA(2)s) are highly myotoxic and cause extensive tissue damage despite not showing measurable catalytic activity. They are found in different snake venoms and represent one third of bothropic venom composition. The importance of these toxins during envenomation is related to the pronounced local myotoxic effect they induce since this effect is not neutralized by serum therapy. We present herein three structures of Lys49-PLA(2)s from Bothrops genus snake venom crystallized under the same conditions, two of which were grown in the presence of alpha-tocopherol (vitamin E). Comparative structural analysis of these and other Lys49-PLA(2)s showed two different patterns of oligomeric conformation that are related to the presence or absence of ligands in the hydrophobic channel. This work also confirms the biological dimer indicated by recent studies in which both C-termini are in the dimeric interface. In this configuration, we propose that the myotoxic site of these toxins is composed by the Lys 20, Lys115 and Arg118 residues. For the first time, a residue from the short-helix (Lys20) is suggested as a member of this site and the importance of Tyr119 residue to myotoxicity of bothropic Lys49-PLA(2)s is also discussed. These results support a complete hypothesis for these PLA(2)s myotoxic activity consistent with all findings on bothropic Lys49-PLA(2)s studied up to this moment, including crystallographic, bioinformatics, biochemical and biophysical data.
Comparative structural studies on Lys49-phospholipases A(2) from Bothrops genus reveal their myotoxic site.,dos Santos JI, Soares AM, Fontes MR J Struct Biol. 2009 Aug;167(2):106-16. Epub 2009 May 3. PMID:19401234[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, Soares AM, Fontes MR. Comparative structural studies on Lys49-phospholipases A(2) from Bothrops genus reveal their myotoxic site. J Struct Biol. 2009 Aug;167(2):106-16. Epub 2009 May 3. PMID:19401234 doi:10.1016/j.jsb.2009.04.003
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