1cnn

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OMEGA-CONOTOXIN MVIIC FROM CONUS MAGUSOMEGA-CONOTOXIN MVIIC FROM CONUS MAGUS

Structural highlights

1cnn is a 1 chain structure with sequence from Conus magus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

O17C_CONMA Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels (Cav). This toxin preferentially blocks P/Q-type calcium channels (Cav2.1/CACNA1A) (IC(50)=0.60 nM) (PubMed:1352986, PubMed:10938268). Shows also an inhibition on Cav2.2/CACNA1A channels (IC(50)=7.0 nM) (PubMed:10938268).[1] [2]

Publication Abstract from PubMed

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.

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[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Lewis RJ, Nielsen KJ, Craik DJ, Loughnan ML, Adams DA, Sharpe IA, Luchian T, Adams DJ, Bond T, Thomas L, Jones A, Matheson JL, Drinkwater R, Andrews PR, Alewood PF. Novel omega-conotoxins from Conus catus discriminate among neuronal calcium channel subtypes. J Biol Chem. 2000 Nov 10;275(45):35335-44. PMID:10938268 doi:10.1074/jbc.M002252200
  2. ↑ Hillyard DR, Monje VD, Mintz IM, Bean BP, Nadasdi L, Ramachandran J, Miljanich G, Azimi-Zoonooz A, McIntosh JM, Cruz LJ, et al.. A new Conus peptide ligand for mammalian presynaptic Ca2+ channels. Neuron. 1992 Jul;9(1):69-77. PMID:1352986
  3. ↑ Nielsen KJ, Adams D, Thomas L, Bond T, Alewood PF, Craik DJ, Lewis RJ. Structure-activity relationships of omega-conotoxins MVIIA, MVIIC and 14 loop splice hybrids at N and P/Q-type calcium channels. J Mol Biol. 1999 Jun 25;289(5):1405-21. PMID:10373375 doi:http://dx.doi.org/10.1006/jmbi.1999.2817
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