1hvw

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Revision as of 14:44, 20 November 2007

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HAIRPINLESS MUTANT OF OMEGA-ATRACOTOXIN-HV1A

Overview

omega-Atracotoxin-Hv1a is an insect-specific neurotoxin whose phylogenetic, specificity derives from its ability to antagonize insect, but not, vertebrate, voltage-gated calcium channels. In order to help understand, its mechanism of action and to enhance its utility as a lead compound for, insecticide development, we used a combination of protein engineering and, site-directed mutagenesis to probe the toxin for key functional regions., First, we constructed a Hairpinless mutant in which the C-terminal, beta-hairpin, which is highly conserved in this family of neurotoxins, was, excised without affecting the fold of the residual disulfide-rich core of, the toxin. The Hairpinless mutant was devoid of insecticidal activity, indicating the functional importance of the hairpin. We subsequently, developed a highly efficient system for production of recombinant toxin, and then probed the hairpin for key functional residues using, alanine-scanning mutagenesis followed by a second round of mutagenesis, based on initial "hits" from the alanine scan. This revealed that two, spatially proximal residues, Asn(27) and Arg(35), form a contiguous, molecular surface that is essential for toxin activity. We propose that, this surface of the beta-hairpin is a key site for interaction of the, toxin with insect calcium channels.

About this Structure

1HVW is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.

Reference

Functional significance of the beta hairpin in the insecticidal neurotoxin omega-atracotoxin-Hv1a., Tedford HW, Fletcher JI, King GF, J Biol Chem. 2001 Jul 13;276(28):26568-76. Epub 2001 Apr 19. PMID:11313356

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