1cnn
From Proteopedia
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OMEGA-CONOTOXIN MVIIC FROM CONUS MAGUS
Overview
The omega-conotoxins are a set of structurally related, four-loop, six, cysteine containing peptides, that have a range of selectivities for, different subtypes of the voltage-sensitive calcium channel (VSCC). To, investigate the basis of the selectivity displayed by these peptides, we, have studied the binding affinities of two naturally occurring, omega-conotoxins, MVIIA and MVIIC and a series of 14 MVIIA/MVIIC loop, hybrids using radioligand binding assays for N and P/Q-type Ca2+channels, in rat brain tissue. A selectivity profile was developed from the ratio of, relative potencies at N-type VSCCs (using [125I]GVIA radioligand binding, assays) and P/Q-type VSCCs (using [125I]MVIIC radioligand binding assays)., In these peptides, loops 2 and 4 make the greatest contribution to VSCC, subtype selectivity, while the effects of loops 1 and 3 are negligible., Peptides with homogenous combinations of loop 2 and 4 display clear, selectivity preferences, while those with heterogeneous combinations of, loops 2 and 4 are less discriminatory. 1H NMR spectroscopy revealed that, the global folds of MVIIA, MVIIC and the 14 loop hybrid peptides were, similar; however, several differences in local structure were identified., Based on the binding data and the 3D structures of MVIIA, GVIA and MVIIC, we have developed a preliminary pharmacophore based on the omega-conotoxin, residues most likely to interact with the N-type VSCC.
About this Structure
1CNN is a Single protein structure of sequence from [1] with NH2 as ligand. Full crystallographic information is available from OCA.
Reference
Structure-activity relationships of omega-conotoxins MVIIA, MVIIC and 14 loop splice hybrids at N and P/Q-type calcium channels., Nielsen KJ, Adams D, Thomas L, Bond T, Alewood PF, Craik DJ, Lewis RJ, J Mol Biol. 1999 Jun 25;289(5):1405-21. PMID:10373375
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