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| | ==Crotoxin B, the basic PLA2 from Crotalus durissus terrificus.== | | ==Crotoxin B, the basic PLA2 from Crotalus durissus terrificus.== |
| - | <StructureSection load='2qog' size='340' side='right' caption='[[2qog]], [[Resolution|resolution]] 2.28Å' scene=''> | + | <StructureSection load='2qog' size='340' side='right'caption='[[2qog]], [[Resolution|resolution]] 2.28Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2qog]] is a 4 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=2QOG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QOG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2qog]] is a 4 chain structure with sequence from [https://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=2QOG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QOG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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]] 2.28Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ok9|2ok9]], [[2oqd|2oqd]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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'>[https://proteopedia.org/fgij/fg.htm?mol=2qog FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qog OCA], [https://pdbe.org/2qog PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qog RCSB], [https://www.ebi.ac.uk/pdbsum/2qog PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qog ProSAT]</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=2qog FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qog OCA], [http://pdbe.org/2qog PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2qog RCSB], [http://www.ebi.ac.uk/pdbsum/2qog PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2qog ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PA2BA_CRODU PA2BA_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 CBa2: The basic subunit of crotoxin is a snake venom phospholipase A2 (PLA2) that exhibits weak neurotoxicity (10-fold less than the heterodimer) and strong anticoagulant effects by binding to factor Xa (F10) and inhibiting the prothrombinase activity (IC(50) is 41 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> [[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> | + | [https://www.uniprot.org/uniprot/PA2BA_CRODU PA2BA_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 CBa2: The basic subunit of crotoxin is a snake venom phospholipase A2 (PLA2) that exhibits weak neurotoxicity (10-fold less than the heterodimer) and strong anticoagulant effects by binding to factor Xa (F10) and inhibiting the prothrombinase activity (IC(50) is 41 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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qo/2qog_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qo/2qog_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | ==See Also== | | ==See Also== |
| - | *[[Phospholipase A2|Phospholipase A2]] | + | *[[Phospholipase A2 3D structures|Phospholipase A2 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Crotalus durissus terrificus]] | | [[Category: Crotalus durissus terrificus]] |
| - | [[Category: Correa, L C]] | + | [[Category: Large Structures]] |
| - | [[Category: Fontes, M R.M]] | + | [[Category: Correa LC]] |
| - | [[Category: Marchi-Salvador, D P]] | + | [[Category: Fontes MRM]] |
| - | [[Category: Calcium]] | + | [[Category: Marchi-Salvador DP]] |
| - | [[Category: Crotoxin b cd-cdt basic-pla2]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Lipid degradation]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Neurotoxin]]
| + | |
| - | [[Category: Presynaptic neurotoxin]]
| + | |
| - | [[Category: Secreted]]
| + | |
| Structural highlights
Function
PA2BA_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).[1] Monomer CBa2: The basic subunit of crotoxin is a snake venom phospholipase A2 (PLA2) that exhibits weak neurotoxicity (10-fold less than the heterodimer) and strong anticoagulant effects by binding to factor Xa (F10) and inhibiting the prothrombinase activity (IC(50) is 41 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.[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
Crotoxin B (CB or Cdt PLA(2)) is a basic Asp49-PLA(2) found in the venom of Crotalus durissus terrificus and it is one of the subunits that constitute the crotoxin (Cro). This heterodimeric toxin, main component of the C. d. terrificus venom, is completed by an acidic, nontoxic, and nonenzymatic component (crotoxin A, CA or crotapotin), and it is related to important envenomation effects such as neurological disorders, myotoxicity, and renal failure. Although Cro has been crystallized since 1938, no crystal structure of this toxin or its subunits is currently available. In this work, the authors present the crystal structure of a novel tetrameric complex formed by two dimers of crotoxin B isoforms (CB1 and CB2). The results suggest that these assemblies are stable in solution and show that Ser1 and Glu92 of CB1 and CB2, respectively, play an important role in the oligomerization. The tetrameric and dimeric conformations resulting from the association of the isoforms may increase the neurotoxicity of the toxin CB by the creation of new binding sites, which could improve the affinity of the molecular complexes to the presynaptic membrane. Proteins 2008. (c) 2008 Wiley-Liss, Inc.
Insights into the role of oligomeric state on the biological activities of crotoxin: Crystal structure of a tetrameric phospholipase A(2) formed by two isoforms of crotoxin B from Crotalus durissus terrificus venom.,Marchi-Salvador DP, Correa LC, Magro AJ, Oliveira CZ, Soares AM, Fontes MR Proteins. 2008 Feb 14;. PMID:18275084[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sampaio SC, Hyslop S, Fontes MR, Prado-Franceschi J, Zambelli VO, Magro AJ, Brigatte P, Gutierrez VP, Cury Y. Crotoxin: novel activities for a classic beta-neurotoxin. Toxicon. 2010 Jun 1;55(6):1045-60. doi: 10.1016/j.toxicon.2010.01.011. Epub 2010 , Jan 28. PMID:20109480 doi:http://dx.doi.org/10.1016/j.toxicon.2010.01.011
- ↑ Faure G, Gowda VT, Maroun RC. Characterization of a human coagulation factor Xa-binding site on Viperidae snake venom phospholipases A2 by affinity binding studies and molecular bioinformatics. BMC Struct Biol. 2007 Dec 6;7:82. PMID:18062812 doi:http://dx.doi.org/10.1186/1472-6807-7-82
- ↑ Marchi-Salvador DP, Correa LC, Magro AJ, Oliveira CZ, Soares AM, Fontes MR. Insights into the role of oligomeric state on the biological activities of crotoxin: Crystal structure of a tetrameric phospholipase A(2) formed by two isoforms of crotoxin B from Crotalus durissus terrificus venom. Proteins. 2008 Feb 14;. PMID:18275084 doi:10.1002/prot.21980
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