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| | <StructureSection load='4v1d' size='340' side='right'caption='[[4v1d]], [[Resolution|resolution]] 3.10Å' scene=''> | | <StructureSection load='4v1d' size='340' side='right'caption='[[4v1d]], [[Resolution|resolution]] 3.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4v1d]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Centruroides_noxius Centruroides noxius] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4V1D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4V1D FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4v1d]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Centruroides_noxius Centruroides noxius] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4V1D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4V1D FirstGlance]. <br> |
| - | </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=4v1d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4v1d OCA], [http://pdbe.org/4v1d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4v1d RCSB], [http://www.ebi.ac.uk/pdbsum/4v1d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4v1d ProSAT]</span></td></tr> | + | </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=4v1d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4v1d OCA], [https://pdbe.org/4v1d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4v1d RCSB], [https://www.ebi.ac.uk/pdbsum/4v1d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4v1d ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SCX2_CENNO SCX2_CENNO]] Mammal beta-toxins bind voltage-independently at site-4 of sodium channels and shift the activation voltage to more negative potentials. This toxin is active against mammals. | + | [https://www.uniprot.org/uniprot/SCX2_CENNO SCX2_CENNO] Mammal beta-toxins bind voltage-independently at site-4 of sodium channels and shift the activation voltage to more negative potentials. This toxin is active against mammals. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| | *[[Antibody 3D structures|Antibody 3D structures]] | | *[[Antibody 3D structures|Antibody 3D structures]] |
| | + | *[[3D structures of human antibody|3D structures of human antibody]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Centruroides noxius]] | | [[Category: Centruroides noxius]] |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Becerril, B]] | + | [[Category: Becerril B]] |
| - | [[Category: Riano-Umbarila, L]] | + | [[Category: Riano-Umbarila L]] |
| - | [[Category: Rojas-Trejo, S]] | + | [[Category: Rojas-Trejo S]] |
| - | [[Category: Rudino-Pinera, E]] | + | [[Category: Rudino-Pinera E]] |
| - | [[Category: Serrano-Posada, H]] | + | [[Category: Serrano-Posada H]] |
| - | [[Category: Cn2 toxin]]
| + | |
| - | [[Category: Directed evolution]]
| + | |
| - | [[Category: Human scfv]]
| + | |
| - | [[Category: Scorpion venom neutralization]]
| + | |
| - | [[Category: Toxin-immune system complex]]
| + | |
| Structural highlights
Function
SCX2_CENNO Mammal beta-toxins bind voltage-independently at site-4 of sodium channels and shift the activation voltage to more negative potentials. This toxin is active against mammals.
Publication Abstract from PubMed
Nowadays, the trends in the research devoted to develop novel antidotes against scorpion stings have showed excellent results with the use of recombinant antibody fragments. The polyclonal character of commercial anti-venoms, obtained through the immunization of animals and which contain several neutralizing antibodies that recognize different epitopes on the toxins, guarantees the neutralization of the venoms. To avoid the use of animals we aimed to develop an equivalent recombinant anti-venom composed of a few neutralizing single chain antibody fragments (scFvs) that bind to two different epitopes on the scorpion toxins. In this study, we obtained scFv RU1 derived from scFv C1. RU1 showed a good capacity to neutralize the Cn2 toxin and whole venom of the scorpionCentruroides noxius. Previously, we had produced scFv LR, obtained from a different parental fragment (scFv 3F). LR also showed a similar neutralizing capacity. The simultaneous administration of both scFvs resulted in improved protection, which was translated as a rapid recovery of previously envenomed animals. The crystallographic structure of the ternary complex (scFv LR-Cn2-scFv RU1) allowed us to identify the areas of interaction of both scFvs with the toxin, which correspond to non-overlapping sites. The epitope recognized by scFv RU1 seems to be related to a greater efficiency in the neutralization of the whole venom. In addition, the structural analysis of the complex helped us to explain the cross-reactivity of these scFvs and how they neutralize the venom.
Optimal neutralization of Centruroides noxius venom is understood through a structural complex between two antibody fragments and the Cn2 toxin.,Riano-Umbarila L, Ledezma-Candanoza LM, Serrano-Posada H, Fernandez-Taboada G, Olamendi-Portugal T, Rojas-Trejo S, Gomez-Ramirez IV, Rudino-Pinera E, Possani LD, Becerril B J Biol Chem. 2015 Nov 20. pii: jbc.M115.685297. PMID:26589800[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Riano-Umbarila L, Ledezma-Candanoza LM, Serrano-Posada H, Fernandez-Taboada G, Olamendi-Portugal T, Rojas-Trejo S, Gomez-Ramirez IV, Rudino-Pinera E, Possani LD, Becerril B. Optimal neutralization of Centruroides noxius venom is understood through a structural complex between two antibody fragments and the Cn2 toxin. J Biol Chem. 2015 Nov 20. pii: jbc.M115.685297. PMID:26589800 doi:http://dx.doi.org/10.1074/jbc.M115.685297
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