1CNN

OMEGA-CONOTOXIN MVIIC FROM CONUS MAGUS

Summary for 1CNN

• Entry DOI: 10.2210/pdb1cnn/pdb
• NMR Information: BMRB: 4500
• Descriptor: OMEGA-CONOTOXIN MVIIC (1 entity in total)
• Functional Keywords: voltage-sensitive calcium channel antagonist, peptide hybrids, toxin
• Cellular location: Secreted: P37300
• Total number of polymer chains: 1
• Total formula weight: 2761.35

Authors

Nielsen, K.J.,Adams, D.,Thomas, L.,Bond, T.,Alewood, P.F.,Craik, D.J.,Lewis, R.J. (deposition date: 1999-05-20, release date: 2000-05-31, Last modification date: 2024-11-13)

Primary citation

Nielsen, K.J.,Adams, D.,Thomas, L.,Bond, T.,Alewood, P.F.,Craik, D.J.,Lewis, R.J.
Structure-activity relationships of omega-conotoxins MVIIA, MVIIC and 14 loop splice hybrids at N and P/Q-type calcium channels.
J.Mol.Biol., 289:1405-1421, 1999

PubMed Abstract: 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.

PubMed: 10373375
DOI: 10.1006/jmbi.1999.2817

Experimental method

SOLUTION NMR