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1mvj

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1mvj

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N-TYPE CALCIUM CHANNEL BLOCKER, OMEGA-CONOTOXIN MVIIA NMR, 15 STRUCTURES

Overview

The omega-conotoxins are a set of structurally related peptides that have, a wide range of specificities for different subtypes of the, voltage-sensitive calcium channel (VSCC). To understand their VSCC subtype, differentiation we studied the structure of two naturally occurring, omega-conotoxins, MVIIA (specific to N-type) and SVIB (specific to, P/Q-type) and a synthetic hybrid, SNX-202, which has altered specificities, to both VSCC subtypes. The secondary structures of the three peptides are, almost identical, consisting of a triple-stranded beta-sheet and several, turns. A comparison of NMR data emphasizes the structural similarities, between the peptides and highlights some minor structural differences. In, the three-dimensional structures of SVIB and MVIIA these are manifested as, orientational differences between two key loops. The structural rigidity, of MVIIA was also examined. H alpha shifts are similar in a range of, solvents, indicating that there are no solvent-induced changes in, structure. The omega-conotoxins form a consensus structure despite, differences in sequence and VSCC subtype specificity. This indicates that, the omega-conotoxin macrosites for the N/P/Q-subfamily of VSCCs are, related, with specificity for receptor targets being conferred by the, positions of functional side-chains on the surface of the peptides.

About this Structure

1MVJ is a Single protein structure of sequence from Conus striatus with NH2 as ligand. Full crystallographic information is available from OCA.

Reference

A consensus structure for omega-conotoxins with different selectivities for voltage-sensitive calcium channel subtypes: comparison of MVIIA, SVIB and SNX-202., Nielsen KJ, Thomas L, Lewis RJ, Alewood PF, Craik DJ, J Mol Biol. 1996 Oct 25;263(2):297-310. PMID:8913308

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