1zvg
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(New page: 200px<br /><applet load="1zvg" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zvg, resolution 1.20Å" /> '''Crystal Structure Of...)
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Revision as of 05:33, 21 November 2007
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Crystal Structure Of Mutant K8DP9S Of Scorpion alpha-Like Neurotoxin Bmk M1 From Buthus Martensii Karsch
Overview
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.
About this Structure
1ZVG is a Single protein structure of sequence from Mesobuthus martensii. Full crystallographic information is available from OCA.
Reference
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
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