Jingzhaotoxin III

Jingzhaotoxin-III (JZTX-III, molecular weight 3919.3 Da) is a peptide toxin containing 36 amino acid residues with three disulfide bridges crosslinked in the pattern of I–IV, II–V, and III–VI (Cys4–Cys19, Cys11–Cys24, and Cys18–Cys31). In previous study, JZTX-III was found to specifically inhibit Nav channels of rat cardiac myocytes with an IC50 of 0.38 μM and followed by shifting activated voltage in a depolarizing direction, on the other hand, JZTX-III is ineffective on Cav and Navchannels of rat DRG cells, thus, JZTX-III might be an ideal tool for analysis of the Nav channels of cardiac myocytes and for pharmacologic exploitation on cardiac related disease.  >> Read More

Jingzhaotoxin-III (JZTX-III) is a peptide toxin isolated from the venom of the Chinese spider Chilobrachys jingzhao that inhibits Nav channels of rat cardiac myocytes by modifying voltage-dependent gating and also binds to Kv2.1 channel (Kd=0.43 μM) with an action model similar to that of hanatoxin1 and SGTx1. The solution structure of JZTX-III was determined by 1H 2D NMR method. The toxin adopts an ICK motif composed of three β-strands connected by four turns. Structural comparison of JZTX-III with those of other ICK motif peptides shows that they all adopt a conserved surface profile, a hydrophobic patch surrounded by charged residues, which might be the crucial site for voltage-gating ion channel inhibition. Furthermore, the similar action model of JZTX-III affecting both Kv and Nav channels implies that JZTX-III recognized a conserved receptor within the voltage sensing domains, which is similar to that of hanatoxin1 binding to both Kv and Cav channels.

Solution structure of Jingzhaotoxin-III, a peptide toxin inhibiting both Nav1.5 and Kv2.1 channels