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| | ==Crystal Structure Of Mutant K8DP9S Of Scorpion alpha-Like Neurotoxin Bmk M1 From Buthus Martensii Karsch== | | ==Crystal Structure Of Mutant K8DP9S Of Scorpion alpha-Like Neurotoxin Bmk M1 From Buthus Martensii Karsch== |
| - | <StructureSection load='1zvg' size='340' side='right' caption='[[1zvg]], [[Resolution|resolution]] 1.20Å' scene=''> | + | <StructureSection load='1zvg' size='340' side='right'caption='[[1zvg]], [[Resolution|resolution]] 1.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1zvg]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Buthus_martensi Buthus martensi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZVG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ZVG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1zvg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Buthus_martensi Buthus martensi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZVG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZVG FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1zu3|1zu3]], [[1zut|1zut]], [[1zve|1zve]]</td></tr> | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1zu3|1zu3]], [[1zut|1zut]], [[1zve|1zve]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BMK M1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=34649 Buthus martensi])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BMK M1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=34649 Buthus martensi])</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=1zvg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zvg OCA], [http://pdbe.org/1zvg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1zvg RCSB], [http://www.ebi.ac.uk/pdbsum/1zvg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1zvg 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=1zvg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zvg OCA], [https://pdbe.org/1zvg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zvg RCSB], [https://www.ebi.ac.uk/pdbsum/1zvg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zvg ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SCX1_MESMA SCX1_MESMA]] This alpha-like toxin binds voltage-dependently sodium channels and inhibits the inactivation of the activated channels, thereby blocking neuronal transmission. This toxin is active against mammals and insects. Is active on Nav1.4/SCN4A and Nav1.5/SCN5A. Acts as a cardiotoxin. Is 6-fold more toxic than BmK-M2.<ref>PMID:11322948</ref> <ref>PMID:12705833</ref> | + | [[https://www.uniprot.org/uniprot/SCX1_MESMA SCX1_MESMA]] This alpha-like toxin binds voltage-dependently sodium channels and inhibits the inactivation of the activated channels, thereby blocking neuronal transmission. This toxin is active against mammals and insects. Is active on Nav1.4/SCN4A and Nav1.5/SCN5A. Acts as a cardiotoxin. Is 6-fold more toxic than BmK-M2.<ref>PMID:11322948</ref> <ref>PMID:12705833</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Buthus martensi]] | | [[Category: Buthus martensi]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Bosmans, F]] | | [[Category: Bosmans, F]] |
| | [[Category: Li, C]] | | [[Category: Li, C]] |
| Structural highlights
Function
[SCX1_MESMA] This alpha-like toxin binds voltage-dependently sodium channels and inhibits the inactivation of the activated channels, thereby blocking neuronal transmission. This toxin is active against mammals and insects. Is active on Nav1.4/SCN4A and Nav1.5/SCN5A. Acts as a cardiotoxin. Is 6-fold more toxic than BmK-M2.[1] [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
Scorpion alpha-like toxins are proteins that act on mammalian and insect voltage-gated Na+ channels. Therefore, these toxins constitute an excellent target for examining the foundations that underlie their target specificity. With this motive we dissected the role of six critical amino acids located in the five-residue reverse turn (RT) and C-tail (CT) of the scorpion alpha-like toxin BmK M1. These residues were individually substituted resulting in 11 mutants and were subjected to a bioassay on mice, an electrophysiological characterization on three cloned voltage-gated Na+ channels (Nav1.2, Nav1.5 and para), a CD analysis and X-ray crystallography. The results reveal two molecular sites, a couplet of residues (8-9) in the RT and a hydrophobic surface consisting of residues 57 and 59-61 in the CT, where the substitution with specific residues can redirect the alpha-like characteristics of BmK M1 to either total insect or much higher mammal specificity. Crystal structures reveal that the pharmacological ramification of these mutants is accompanied by the reshaping of the 3D structure surrounding position 8. Furthermore, our results also reveal that residues 57 and 59-61, located at the CT, enclose the critical residue 58 in order to form a hydrophobic "gasket". Mutants of BmK M1 that interrupt this hydrophobic surface significantly gain insect selectivity.
Structural basis for the voltage-gated Na+ channel selectivity of the scorpion alpha-like toxin BmK M1.,Ye X, Bosmans F, Li C, Zhang Y, Wang DC, Tytgat J J Mol Biol. 2005 Nov 4;353(4):788-803. Epub 2005 Sep 22. PMID:16209876[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Goudet C, Huys I, Clynen E, Schoofs L, Wang DC, Waelkens E, Tytgat J. Electrophysiological characterization of BmK M1, an alpha-like toxin from Buthus martensi Karsch venom. FEBS Lett. 2001 Apr 20;495(1-2):61-5. PMID:11322948
- ↑ Wang CG, Gilles N, Hamon A, Le Gall F, Stankiewicz M, Pelhate M, Xiong YM, Wang DC, Chi CW. Exploration of the functional site of a scorpion alpha-like toxin by site-directed mutagenesis. Biochemistry. 2003 Apr 29;42(16):4699-708. PMID:12705833 doi:http://dx.doi.org/10.1021/bi0270438
- ↑ Ye X, Bosmans F, Li C, Zhang Y, Wang DC, Tytgat J. Structural basis for the voltage-gated Na+ channel selectivity of the scorpion alpha-like toxin BmK M1. J Mol Biol. 2005 Nov 4;353(4):788-803. Epub 2005 Sep 22. PMID:16209876 doi:10.1016/j.jmb.2005.08.068
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