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1zut

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Revision as of 09:18, 2 May 2018

Crystal Structure Of Mutant K8DP9SR58K Of Scorpion alpha-Like Neurotoxin Bmk M1 From Buthus Martensii Karsch

Structural highlights

1zut is a 1 chain structure with sequence from Buthus martensi. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1zu3, 1zve, 1zvg
Gene:	BMK M1 (Buthus martensi)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1zut"

@@ Line 1: / Line 1: @@
 ==Crystal Structure Of Mutant K8DP9SR58K Of Scorpion alpha-Like Neurotoxin Bmk M1 From Buthus Martensii Karsch==
 <StructureSection load='1zut' size='340' side='right' caption='[[1zut]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1zu3|1zu3]], [[1zve|1zve]], [[1zvg|1zvg]]</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='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=1zut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zut OCA], [http://pdbe.org/1zut PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1zut RCSB], [http://www.ebi.ac.uk/pdbsum/1zut PDBsum]</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=1zut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zut OCA], [http://pdbe.org/1zut PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1zut RCSB], [http://www.ebi.ac.uk/pdbsum/1zut PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1zut ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zu/1zut_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zu/1zut_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

1zut

From Proteopedia

Revision as of 09:18, 2 May 2018

Crystal Structure Of Mutant K8DP9SR58K Of Scorpion alpha-Like Neurotoxin Bmk M1 From Buthus Martensii Karsch

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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