Kaliotoxin (KTX) is an
ion channel toxinwhich inhibits potassium flux through the Kv1.3 voltage-gated potassium channeland calcium-activated potassium channels by physically blocking the channel-entrance and secondly KTX induces a conformational changein the K+-selectivity filter of the channel.
KTX is a
neurotoxinderived from the scorpion Androctonus mauretanicus mauretanicus, which is found in the Middle Eastand North Africa.
Kaliotoxin is a 4-kDa polypeptide chain containing 37
amino acids. The sequence has a large homologywith iberiotoxinfrom "Buthus tumulus", charybdotoxinfrom "Leiurus quinquestriatus" and noxiustoxin from "Centruroides noxius".An Important site of the toxin is the K27 side chain (a lysineon place 27 of the protein sequence), which enters the pore and protrudes into the selectivity filter of the channel.
KTX is a high
affinitytoxin, which binds to the Kv1.3 voltage-gated potassium channeland high conductance Calcium activated potassium channels (BK channels). These channels control several regulating processes, including neurotransmitterrelease, heart rate, insulinsecretion, smooth musclecontraction.
Mode of action
The toxin binds to the potassium channel on the
extracellularsurface not voltage dependent. The configuration of the toxin fits onto the channel with the K27 side chain protruding into the pore and plugging it by conformational change of the toxin. The positively charged amino-group of the K27 chain fits into the selectivity filter near the G77 ( Glycine) chain of the channel causing a conformational change of the channels selectivity filter. Thereby the hydrophobicgroups of the K27 side chain replace water molecules in the entry region of the pore.So the pore is blocked by a direct plug into the pore region of the channel and a conformational change in the selectivity filter is induced.
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