1av3
From Proteopedia
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POTASSIUM CHANNEL BLOCKER KAPPA CONOTOXIN PVIIA FROM C. PURPURASCENS, NMR, 20 STRUCTURES
Overview
BACKGROUND: kappa-PVIIA is a 27-residue polypeptide isolated from the, venom of Conus purpurascens and is the first member of a new class of, conotoxins that block potassium channels. By comparison to other ion, channels of eukaryotic cell membranes, voltage-sensitive potassium, channels are relatively simple and methodology has been developed for, mapping their interactions with small-peptide toxins. PVIIA, therefore, is, a valuable new probe of potassium channel structure. This study of the, solution structure and mode of channel binding of PVIIA forms the basis, for mapping the interacting residues at the conotoxin-ion channel, interface. RESULTS: The three-dimensional structure of PVIIA resembles the, triple-stranded beta sheet/cystine-knot motif formed by a number of toxic, and inhibitory peptides. Subtle structural differences, predominantly in, loops 2 and 4, are observed between PVIIA and other conotoxins with, similar structural frameworks, however. Electrophysiological binding data, suggest that PVIIA blocks channel currents by binding in a, voltage-sensitive manner to the external vestibule and occluding the pore., Comparison of the electrostatic surface of PVIIA with that of the, well-characterised potassium channel blocker charybdotoxin suggests a, likely binding orientation for PVIIA. CONCLUSIONS: Although the structure, of PVIIA is considerably different to that of the alphaK scorpion toxins, it has a similar mechanism of channel blockade. On the basis of a, comparison of the structures of PVIIA and charybdotoxin, we suggest that, Lys19 of PVIIA is the residue which is responsible for physically, occluding the pore of the potassium channel.
About this Structure
1AV3 is a Single protein structure of sequence from Conus purpurascens. Full crystallographic information is available from OCA.
Reference
Solution structure and proposed binding mechanism of a novel potassium channel toxin kappa-conotoxin PVIIA., Scanlon MJ, Naranjo D, Thomas L, Alewood PF, Lewis RJ, Craik DJ, Structure. 1997 Dec 15;5(12):1585-97. PMID:9438859
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