1hvw

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[[Image:1hvw.gif|left|200px]]
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{{Seed}}
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[[Image:1hvw.png|left|200px]]
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{{STRUCTURE_1hvw| PDB=1hvw | SCENE= }}
{{STRUCTURE_1hvw| PDB=1hvw | SCENE= }}
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'''HAIRPINLESS MUTANT OF OMEGA-ATRACOTOXIN-HV1A'''
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===HAIRPINLESS MUTANT OF OMEGA-ATRACOTOXIN-HV1A===
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==Overview==
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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.
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The line below this paragraph, {{ABSTRACT_PUBMED_11313356}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 11313356 is the PubMed ID number.
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{{ABSTRACT_PUBMED_11313356}}
==About this Structure==
==About this Structure==
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1HVW is a [[Single protein]] structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HVW OCA].
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1HVW is a [[Single protein]] structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HVW OCA].
==Reference==
==Reference==
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[[Category: Beta-hairpin]]
[[Category: Beta-hairpin]]
[[Category: Cystine knot]]
[[Category: Cystine knot]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 19:17:00 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 08:53:39 2008''

Revision as of 05:53, 1 July 2008

Image:1hvw.png

Template:STRUCTURE 1hvw

HAIRPINLESS MUTANT OF OMEGA-ATRACOTOXIN-HV1A

Template:ABSTRACT PUBMED 11313356

About this Structure

1HVW is a Single protein structure. Full experimental 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

Page seeded by OCA on Tue Jul 1 08:53:39 2008

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