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| | ==Crystal Structure of MT-I isolated from Bothrops asper venom.== | | ==Crystal Structure of MT-I isolated from Bothrops asper venom.== |
| - | <StructureSection load='5tfv' size='340' side='right' caption='[[5tfv]], [[Resolution|resolution]] 2.54Å' scene=''> | + | <StructureSection load='5tfv' size='340' side='right'caption='[[5tfv]], [[Resolution|resolution]] 2.54Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5tfv]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bothrops_asper Bothrops asper]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TFV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TFV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5tfv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bothrops_asper Bothrops asper]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TFV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TFV FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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]] 2.54Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phospholipase_A(2) Phospholipase A(2)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.4 3.1.1.4] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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=5tfv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tfv OCA], [http://pdbe.org/5tfv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tfv RCSB], [http://www.ebi.ac.uk/pdbsum/5tfv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tfv 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=5tfv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tfv OCA], [https://pdbe.org/5tfv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tfv RCSB], [https://www.ebi.ac.uk/pdbsum/5tfv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tfv ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PA2B3_BOTAS PA2B3_BOTAS]] Snake venom phospholipase A2 (PLA2) that displays local myotoxic activity and induces a dose-dependent edema. Myotoxic activity is probably related to a molecular region different from the catalytic site, although enzymatic activity greatly enhances myotoxin action. PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.<ref>PMID:2327788</ref> <ref>PMID:6426093</ref> <ref>PMID:8218369</ref> <ref>PMID:8456450</ref> <ref>PMID:9839670</ref> | + | [https://www.uniprot.org/uniprot/PA2B3_BOTAS PA2B3_BOTAS] Snake venom phospholipase A2 (PLA2) that displays local myotoxic activity and induces a dose-dependent edema. Myotoxic activity is probably related to a molecular region different from the catalytic site, although enzymatic activity greatly enhances myotoxin action. PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.<ref>PMID:2327788</ref> <ref>PMID:6426093</ref> <ref>PMID:8218369</ref> <ref>PMID:8456450</ref> <ref>PMID:9839670</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Bothrops asper]] | | [[Category: Bothrops asper]] |
| - | [[Category: Fontes, M R.M]] | + | [[Category: Large Structures]] |
| - | [[Category: Salvador, G H.M]] | + | [[Category: Fontes MRM]] |
| - | [[Category: Santos, J I.dos]] | + | [[Category: Salvador GHM]] |
| - | [[Category: Myotoxic asp49-pla2]] | + | [[Category: Dos Santos JI]] |
| - | [[Category: Myotoxin]]
| + | |
| - | [[Category: Toxin]]
| + | |
| Structural highlights
Function
PA2B3_BOTAS Snake venom phospholipase A2 (PLA2) that displays local myotoxic activity and induces a dose-dependent edema. Myotoxic activity is probably related to a molecular region different from the catalytic site, although enzymatic activity greatly enhances myotoxin action. PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
Snake venoms from the Viperidae and Elapidae families often have several phospholipases A2 (PLA2s), which may display different functions despite having a similar structural scaffold. These proteins are considered an important target for the development of drugs against local myotoxic damage because they are not efficiently neutralized by conventional serum therapy. PLA2s from these venoms are generally divided into two classes: (i) catalytic PLA2s (or Asp49-PLA2s) and (ii) non-catalytic PLA2-like toxins (or Lys49-PLA2s). In many Viperidae venoms, a subset of the basic Asp49-PLA2s displays some functional and structural characteristics of PLA2-like proteins and group within the same phylogenetic clade, but their myotoxic mechanism is still largely unknown. In the present study, we have crystallized and solved the structure of myotoxin I (MT-I), a basic myotoxic Asp49-PLA2 isolated from Bothrops asper venom. The structure presents a dimeric conformation that is compatible with that of previous dimers found for basic myotoxic Asp49-PLA2s and Lys49-PLA2s and has been confirmed by other biophysical and bioinformatics techniques. This arrangement suggests a possible cooperative action between both monomers to exert myotoxicity via two different sites forming a putative membrane-docking site (MDoS) and a putative membrane disruption site (MDiS). This mechanism would resemble that proposed for Lys49-PLA2s, but the sites involved appear to be situated in a different region. Thus, as both sites are close to one another, they form a "myotoxic cluster", which is also found in two other basic myotoxic Asp49-PLA2s from Viperidae venoms. Such arrangement may represent a novel structural strategy for the mechanism of muscle damage exerted by the group of basic, Asp49-PLA2s found in viperid snake venoms.
Crystal structure of a phospholipase A2 from Bothrops asper venom: Insights into a new putative "myotoxic cluster".,Salvador GH, Dos Santos JI, Lomonte B, Fontes MR Biochimie. 2017 Feb;133:95-102. doi: 10.1016/j.biochi.2016.12.015. Epub 2016 Dec , 27. PMID:28034717[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kaiser II, Gutierrez JM, Plummer D, Aird SD, Odell GV. The amino acid sequence of a myotoxic phospholipase from the venom of Bothrops asper. Arch Biochem Biophys. 1990 May 1;278(2):319-25. PMID:2327788
- ↑ Gutierrez JM, Ownby CL, Odell GV. Isolation of a myotoxin from Bothrops asper venom: partial characterization and action on skeletal muscle. Toxicon. 1984;22(1):115-28. PMID:6426093
- ↑ Butron E, Ghelestam M, Gutierrez JM. Effects on cultured mammalian cells of myotoxin III, a phospholipase A2 isolated from Bothrops asper (terciopelo) venom. Biochim Biophys Acta. 1993 Nov 24;1179(3):253-9. PMID:8218369
- ↑ Bultron E, Gutierrez JM, Thelestam M. Effects of Bothrops asper (terciopelo) myotoxin III, a basic phospholipase A2, on liposomes and mouse gastrocnemius muscle. Toxicon. 1993 Feb;31(2):217-22. PMID:8456450
- ↑ Chaves F, Leon G, Alvarado VH, Gutierrez JM. Pharmacological modulation of edema induced by Lys-49 and Asp-49 myotoxic phospholipases A2 isolated from the venom of the snake Bothrops asper (terciopelo). Toxicon. 1998 Dec;36(12):1861-9. PMID:9839670
- ↑ Salvador GH, Dos Santos JI, Lomonte B, Fontes MR. Crystal structure of a phospholipase A2 from Bothrops asper venom: Insights into a new putative "myotoxic cluster". Biochimie. 2017 Feb;133:95-102. doi: 10.1016/j.biochi.2016.12.015. Epub 2016 Dec , 27. PMID:28034717 doi:http://dx.doi.org/10.1016/j.biochi.2016.12.015
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