|
|
| Line 3: |
Line 3: |
| | <StructureSection load='3mlm' size='340' side='right'caption='[[3mlm]], [[Resolution|resolution]] 2.21Å' scene=''> | | <StructureSection load='3mlm' size='340' side='right'caption='[[3mlm]], [[Resolution|resolution]] 2.21Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3mlm]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bothrops_neuwiedi_pauloensis Bothrops neuwiedi pauloensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MLM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MLM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3mlm]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bothrops_pauloensis Bothrops pauloensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MLM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MLM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.21Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Phospholipase_A(2) Phospholipase A(2)], with EC number [https://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=MYR:MYRISTIC+ACID'>MYR</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'>[https://proteopedia.org/fgij/fg.htm?mol=3mlm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mlm OCA], [https://pdbe.org/3mlm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mlm RCSB], [https://www.ebi.ac.uk/pdbsum/3mlm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mlm 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=3mlm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mlm OCA], [https://pdbe.org/3mlm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mlm RCSB], [https://www.ebi.ac.uk/pdbsum/3mlm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mlm ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/PA2H_BOTPA PA2H_BOTPA]] Snake venom phospholipase A2 (PLA2) that lacks enzymatic activity. Is myotoxic. Displays bactericidal activity and promotes the blockage of the neuromuscular contraction of the chick biventer cervicis muscle. Also disrupts artificial membranes, and provokes tissue damages characterized by edema, necrosis and inflammation. May act as pro-inflammatory mediators, inducing metalloproteinase and cytokine production from the inflammatory and satellite cells.<ref>PMID:10860537</ref> <ref>PMID:9972319</ref> <ref>PMID:14623331</ref>
| + | [https://www.uniprot.org/uniprot/PA2H_BOTPA PA2H_BOTPA] Snake venom phospholipase A2 (PLA2) that lacks enzymatic activity. Is myotoxic. Displays bactericidal activity and promotes the blockage of the neuromuscular contraction of the chick biventer cervicis muscle. Also disrupts artificial membranes, and provokes tissue damages characterized by edema, necrosis and inflammation. May act as pro-inflammatory mediators, inducing metalloproteinase and cytokine production from the inflammatory and satellite cells.<ref>PMID:10860537</ref> <ref>PMID:9972319</ref> <ref>PMID:14623331</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 26: |
Line 26: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bothrops neuwiedi pauloensis]] | + | [[Category: Bothrops pauloensis]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Cavada, B S]] | + | [[Category: Cavada BS]] |
| - | [[Category: Delatorre, P]] | + | [[Category: Delatorre P]] |
| - | [[Category: Gadelha, C A.A]] | + | [[Category: Gadelha CAA]] |
| - | [[Category: Rocha, B A.M]] | + | [[Category: Rocha BAM]] |
| - | [[Category: Toyama, D]] | + | [[Category: Toyama D]] |
| - | [[Category: Toyama, M H]] | + | [[Category: Toyama MH]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Myotoxin]]
| + | |
| - | [[Category: Phospholipase-like protein]]
| + | |
| Structural highlights
Function
PA2H_BOTPA Snake venom phospholipase A2 (PLA2) that lacks enzymatic activity. Is myotoxic. Displays bactericidal activity and promotes the blockage of the neuromuscular contraction of the chick biventer cervicis muscle. Also disrupts artificial membranes, and provokes tissue damages characterized by edema, necrosis and inflammation. May act as pro-inflammatory mediators, inducing metalloproteinase and cytokine production from the inflammatory and satellite cells.[1] [2] [3]
Publication Abstract from PubMed
The LYS49-PLAs myotoxins have attracted attention as models for the induction of myonecrosis by a catalytically independent mechanism of action. Structural studies and biological activities have demonstrated that the myotoxic activity of LYS49-PLA is independent of the catalytic activity site. The myotoxic effect is conventionally thought to be to due to the C-terminal region 111-121, which plays an effective role in membrane damage. In the present study, Bn IV LYS49-PLA was isolated from Bothrops neuwiedi snake venom in complex with myristic acid (CH(CH)COOH) and its overall structure was refined at 2.2 A resolution. The Bn IV crystals belong to monoclinic space group P2 and contain a dimer in the asymmetric unit. The unit cell parameters are a = 38.8, b = 70.4, c = 44.0 A. The biological assembly is a "conventional dimer" and the results confirm that dimer formation is not relevant to the myotoxic activity. Electron density map analysis of the Bn IV structure shows clearly the presence of myristic acid in catalytic site. The relevant structural features for myotoxic activity are located in the C-terminal region and the Bn IV C-terminal residues NKKYRY are a probable heparin binding domain. These findings indicate that the mechanism of interaction between Bn IV and muscle cell membranes is through some kind of cell signal transduction mediated by heparin complexes.
Crystal structure of Bn IV in complex with myristic acid: a Lys49 myotoxic phospholipase A from Bothrops neuwiedi venom.,Delatorre P, Rocha BA, Santi-Gadelha T, Gadelha CA, Toyama MH, Cavada BS Biochimie. 2011 Mar;93(3):513-8. Epub 2010 Nov 22. PMID:21108987[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Soares AM, Guerra-Sa R, Borja-Oliveira CR, Rodrigues VM, Rodrigues-Simioni L, Rodrigues V, Fontes MR, Lomonte B, Gutierrez JM, Giglio JR. Structural and functional characterization of BnSP-7, a Lys49 myotoxic phospholipase A(2) homologue from Bothrops neuwiedi pauloensis venom. Arch Biochem Biophys. 2000 Jun 15;378(2):201-9. PMID:10860537 doi:http://dx.doi.org/10.1006/abbi.2000.1790
- ↑ Rodrigues VM, Soares AM, Mancin AC, Fontes MR, Homsi-Brandeburgo MI, Giglio JR. Geographic variations in the composition of myotoxins from Bothrops neuwiedi snake venoms: biochemical characterization and biological activity. Comp Biochem Physiol A Mol Integr Physiol. 1998 Nov;121(3):215-22. PMID:9972319
- ↑ Magro AJ, Soares AM, Giglio JR, Fontes MR. Crystal structures of BnSP-7 and BnSP-6, two Lys49-phospholipases A(2): quaternary structure and inhibition mechanism insights. Biochem Biophys Res Commun. 2003 Nov 21;311(3):713-20. PMID:14623331
- ↑ Delatorre P, Rocha BA, Santi-Gadelha T, Gadelha CA, Toyama MH, Cavada BS. Crystal structure of Bn IV in complex with myristic acid: a Lys49 myotoxic phospholipase A from Bothrops neuwiedi venom. Biochimie. 2011 Mar;93(3):513-8. Epub 2010 Nov 22. PMID:21108987 doi:10.1016/j.biochi.2010.11.003
|
