1zyw

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{{STRUCTURE_1zyw| PDB=1zyw | SCENE= }}
{{STRUCTURE_1zyw| PDB=1zyw | SCENE= }}
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'''Crystal Structure Of Mutant K8DP9SR58KP60G Of Scorpion alpha-Like Neurotoxin Bmk M1 From Buthus Martensii Karsch'''
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===Crystal Structure Of Mutant K8DP9SR58KP60G Of Scorpion alpha-Like Neurotoxin Bmk M1 From Buthus Martensii Karsch===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_16209876}}
==About this Structure==
==About this Structure==
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[[Category: Mutant]]
[[Category: Mutant]]
[[Category: Scorpion alpha-like toxin]]
[[Category: Scorpion alpha-like toxin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 12:41:11 2008''

Revision as of 09:41, 29 July 2008

Image:1zyw.png

Template:STRUCTURE 1zyw

Crystal Structure Of Mutant K8DP9SR58KP60G Of Scorpion alpha-Like Neurotoxin Bmk M1 From Buthus Martensii Karsch

Template:ABSTRACT PUBMED 16209876

About this Structure

1ZYW 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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