6tmy
From Proteopedia
(Difference between revisions)
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==Crystal structure of isoform CBd of the basic phospholipase A2 subunit of crotoxin from Crotalus durissus terrificus== | ==Crystal structure of isoform CBd of the basic phospholipase A2 subunit of crotoxin from Crotalus durissus terrificus== | ||
| - | <StructureSection load='6tmy' size='340' side='right'caption='[[6tmy]]' scene=''> | + | <StructureSection load='6tmy' size='340' side='right'caption='[[6tmy]], [[Resolution|resolution]] 1.80Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TMY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TMY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6tmy]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Crotalus_durissus_terrificus Crotalus durissus terrificus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TMY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TMY FirstGlance]. <br> |
| - | </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=6tmy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tmy OCA], [http://pdbe.org/6tmy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6tmy RCSB], [http://www.ebi.ac.uk/pdbsum/6tmy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6tmy ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6tmy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tmy OCA], [http://pdbe.org/6tmy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6tmy RCSB], [http://www.ebi.ac.uk/pdbsum/6tmy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6tmy ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/PA2BC_CRODU PA2BC_CRODU]] Heterodimer CA-CB: Crotoxin is a potent presynaptic neurotoxin that possesses phospholipase A2 (PLA2) activity and exerts a lethal action by blocking neuromuscular transmission. It consists of a non-covalent association of a basic and weakly toxic PLA2 subunit (CBa2, CBb, CBc, or CBd), with a small acidic, non-enzymatic and non-toxic subunit (CA1, CA2, CA3 or CA4). The complex acts by binding to a specific 48-kDa protein (R48) receptor located on presynaptic membranes, forming a transient ternary complex CA-CB-R48, followed by dissociation of the CA-CB complex and release of the CA subunit. At equilibrium, only the CB subunits remain associated with the specific crotoxin receptor. In addition to neurotoxicity, crotoxin has been found to exert myotoxicity, nephrotoxicity, and cardiovascular toxicity (PubMed:20109480). Moreover, anti-inflammatory, immunomodulatory, anti-tumor and analgesic effects of crotoxin have also been reported (PubMed:20109480).<ref>PMID:20109480</ref> Monomer CBc: The basic subunit of crotoxin is a snake venom phospholipase A2 (PLA2) that exhibits weak neurotoxicity (10-fold less than the heterodimer) and very strong anticoagulant effects by binding to factor Xa (F10) and inhibiting the prothrombinase activity (IC(50) is 0.7 nM) (PubMed:18062812). In addition, it shows the same effects described for the heterodimer and binds the nucleotide-binding domain (NBD1) of CFTR chloride channels and increases the channel current. PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.<ref>PMID:18062812</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Crotoxin, from the venom of the South American rattlesnake Crotalus durissus terrificus, is a potent heterodimeric presynaptic beta-neurotoxin that exists in individual snake venom as a mixture of isoforms of a basic phospholipase A2 (PLA2) subunit (CBa2, CBb, CBc, and CBd) and acidic subunit (CA1-4). Specific natural mutations in CB isoforms are implicated in functional differences between crotoxin isoforms. The three-dimensional structure of two individual CB isoforms (CBa2, CBc), and one isoform in a crotoxin (CA2CBb) complex, have been previously reported. This study concerns CBd, which by interaction with various protein targets exhibits many physiological or pharmacological functions. It binds with high affinity to presynaptic receptors showing neurotoxicity, but also interacts with human coagulation factor Xa (hFXa), exhibiting anticoagulant effect, and acts as a positive allosteric modulator and corrector of mutated chloride channel, cystic fibrosis transmembrane conductance regulator (CFTR), implicated in cystic fibrosis. Thus, CBd represents a novel family of agents that have potential in identifying new drug leads related to anticoagulant and anti-cystic fibrosis function. We determined here the X-ray structure of CBd and compare it with the three other natural isoforms of CB. The structural role of specific amino acid variations between CB isoforms are analyzed and the structural framework of CB for interaction with protein targets is described. | ||
| + | |||
| + | Crystal Structure of Isoform CBd of the Basic Phospholipase A2 Subunit of Crotoxin: Description of the Structural Framework of CB for Interaction with Protein Targets.,Nemecz D, Ostrowski M, Ravatin M, Saul F, Faure G Molecules. 2020 Nov 13;25(22). pii: molecules25225290. doi:, 10.3390/molecules25225290. PMID:33202772<ref>PMID:33202772</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6tmy" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Crotalus durissus terrificus]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Faure G]] | + | [[Category: Faure, G]] |
| - | [[Category: Nemecz D]] | + | [[Category: Nemecz, D]] |
| - | [[Category: Ostrowski M]] | + | [[Category: Ostrowski, M]] |
| - | [[Category: Saul | + | [[Category: Saul, F A]] |
| + | [[Category: Cb isoform]] | ||
| + | [[Category: Crotoxin]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Presynaptic phospholipase a2]] | ||
Revision as of 06:47, 9 December 2020
Crystal structure of isoform CBd of the basic phospholipase A2 subunit of crotoxin from Crotalus durissus terrificus
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