1mb6
From Proteopedia
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Three dimensional solution structure of huwentoxin-IV by 2D 1H-NMR
Overview
We have isolated a highly potent neurotoxin from the venom of the Chinese, bird spider, Selenocosmia huwena. This 4.1-kDa toxin, which has been named, huwentoxin-IV, contains 35 residues with three disulfide bridges:, Cys-2-Cys-17, Cys-9-Cys-24, and Cys-16-Cys-31, assigned by a chemical, strategy including partial reduction of the toxin and sequence analysis of, the modified intermediates. It specifically inhibits the neuronal, tetrodotoxin-sensitive (TTX-S) voltage-gated sodium channel with the, IC(50) value of 30 nm in adult rat dorsal root ganglion neurons, while, having no significant effect on the tetrodotoxin-resistant (TTX-R), voltage-gated sodium channel. This toxin seems to be a site I toxin, affecting the sodium channel through a mechanism quite similar to that of, TTX: it suppresses the peak sodium current without altering the activation, or inactivation kinetics. The three-dimensional structure of huwentoxin-IV, has been determined by two-dimensional (1)H NMR combined with distant, geometry and simulated annealing calculation by using 527 nuclear, Overhauser effect constraints and 14 dihedral constraints. The resulting, structure is composed of a double-stranded antiparallel beta-sheet, (Leu-22-Ser-25 and Trp-30-Tyr-33) and four turns (Glu-4-Lys-7, Pro-11-Asp-14, Lys-18-Lys-21 and Arg-26-Arg-29) and belongs to the, inhibitor cystine knot structural family. After comparison with other, toxins purified from the same species, we are convinced that the, positively charged residues of loop IV (residues 25-29), especially, residue Arg-26, must be crucial to its binding to the neuronal, tetrodotoxin-sensitive voltage-gated sodium channel.
About this Structure
1MB6 is a Single protein structure of sequence from Ornithoctonus huwena. Full crystallographic information is available from OCA.
Reference
Function and solution structure of huwentoxin-IV, a potent neuronal tetrodotoxin (TTX)-sensitive sodium channel antagonist from Chinese bird spider Selenocosmia huwena., Peng K, Shu Q, Liu Z, Liang S, J Biol Chem. 2002 Dec 6;277(49):47564-71. Epub 2002 Sep 11. PMID:12228241
Page seeded by OCA on Tue Nov 20 21:17:34 2007
