This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


1hvw

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (18:39, 29 November 2023) (edit) (undo)
 
(9 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1hvw.gif|left|200px]]
 
-
<!--
+
==HAIRPINLESS MUTANT OF OMEGA-ATRACOTOXIN-HV1A==
-
The line below this paragraph, containing "STRUCTURE_1hvw", creates the "Structure Box" on the page.
+
<StructureSection load='1hvw' size='340' side='right'caption='[[1hvw]]' scene=''>
-
You may change the PDB parameter (which sets the PDB file loaded into the applet)
+
== Structural highlights ==
-
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+
<table><tr><td colspan='2'>[[1hvw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Hadronyche_versuta Hadronyche versuta]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HVW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HVW FirstGlance]. <br>
-
or leave the SCENE parameter empty for the default display.
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
-
-->
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1hvw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hvw OCA], [https://pdbe.org/1hvw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hvw RCSB], [https://www.ebi.ac.uk/pdbsum/1hvw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hvw ProSAT]</span></td></tr>
-
{{STRUCTURE_1hvw| PDB=1hvw | SCENE= }}
+
</table>
-
 
+
== Function ==
-
'''HAIRPINLESS MUTANT OF OMEGA-ATRACOTOXIN-HV1A'''
+
[https://www.uniprot.org/uniprot/TO1A_HADVE TO1A_HADVE] Reversibly and voltage-independently blocks both mid-low- (M-LVA) and high-voltage-activated (HVA) calcium channels in cockroach DUM neurons (PubMed:17610847). Is lethal to many insect species but not toxic to mammals (PubMed:9228949, PubMed:16779650). May target the insect high-voltage-activated calcium channel Dmca1D. Also inhibits acarines calcium channels. An extremely high toxin concentration partially inhibits Cav1.2/CACNA1C, Cav2.1/CACNA1A and Cav2.2/CACNA1B calcium channel of rats. As for omega-AcTx-Hv2a, the phenotypic effect of injection of this toxin into lone star ticks (Amblyomma americanum) is curling of all eight legs into closed loops.<ref>PMID:14608494</ref> <ref>PMID:15308644</ref> <ref>PMID:16330063</ref> <ref>PMID:17141372</ref> <ref>PMID:17610847</ref> <ref>PMID:9228949</ref>
-
 
+
<div style="background-color:#fffaf0;">
-
 
+
== Publication Abstract from PubMed ==
-
==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.
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==
+
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<ref>PMID:11313356</ref>
-
1HVW is a [[Single protein]] structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HVW OCA].
+
-
==Reference==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
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:[http://www.ncbi.nlm.nih.gov/pubmed/11313356 11313356]
+
</div>
-
[[Category: Single protein]]
+
<div class="pdbe-citations 1hvw" style="background-color:#fffaf0;"></div>
-
[[Category: Fletcher, J I.]]
+
== References ==
-
[[Category: King, G F.]]
+
<references/>
-
[[Category: Beta-hairpin]]
+
__TOC__
-
[[Category: Cystine knot]]
+
</StructureSection>
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 19:17:00 2008''
+
[[Category: Hadronyche versuta]]
 +
[[Category: Large Structures]]
 +
[[Category: Fletcher JI]]
 +
[[Category: King GF]]

Current revision

HAIRPINLESS MUTANT OF OMEGA-ATRACOTOXIN-HV1A

PDB ID 1hvw

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1hvw"
Personal tools