Toxin Name ω-agatoxin-Aa4b
Source Species Agelenopsis  aperta (Western grass spider)
Toxin Group Agatoxin
Description ω-agatoxin-Aa4b is a paralog of the classical Cav2.1 blocker ω-agatoxin-Aa4a (ω-Aga-IVA) that has insecticidal activity. It was simultaneously discovered by groups in Japan and the USA and named ω-agatoxin Tsukuba (ω-Aga-TK) and ω-agatoxin IVB (ω-Aga-IVB). The toxin was subsequently shown to be a post-translationally modified form of ω-agatoxin-Aa4c (ω-Aga-IVC) in which Ser46 is epimerized from the L- to the D-stereoisomer by a novel cofactor-independent peptide isomerase found in the venom. Isomerization of Ser46 to the D-configuration improves the activity of the toxin by ~90-fold against Cav2.1 (P-type) channels in rat cerebellar Purkinje neurons and increases the resistance of the toxin to proteases.

Although the level of identity between the two toxins is only 71%, the specificity and affinity of ω-AGTX-Aa4b for Cav2.1 channels is indistinguishable from that of ω-AGTX-Aa4a, although the kinetics of block are somewhat slower for ω-AGTX-Aa4b. As for ω-AGTX-Aa4a, the disordered C-terminal "tail" is essential for activity. It has been suggested that the role of the "tail" might be to simply anchor the toxins to the cell membrane via interaction with either the lipid bilayer or transmembrane regions of the Cav channel.

The toxin is present in venom at a concentration of 0.8-1.0 mM.
Discovered 1993
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This toxin last updated on Aug 20, 2010

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