1mvi
From Proteopedia
N-TYPE CALCIUM CHANNEL BLOCKER, OMEGA-CONOTOXIN MVIIA, NMR, 15 STRUCTURES
Structural highlights
FunctionO17A_CONMA Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels. This toxin blocks Cav2.2/CACNA1B calcium channels (IC(50)=0.67-208 nM) (PubMed:7826361, PubMed:26344359, PubMed:34589389). It acts by neutralizing the outer electronegativity and sterically hindering the ion access path to the entrance of the channel selectivity filter (PubMed:34234349). It also shows antiproliferative effects on different glioma cell lines (M059J, U-138MG and U-251MG) (PubMed:28202361). In vivo, is lethal to fish (PubMed:26344359, PubMed:34589389). In vivo, injection into mammals induces adverse effects, such as tremor, diminution of spontaneous locomotor activity and bad coordinated locomotion (PubMed:26344359). In addition, it causes reduction of tumor area in the mouse glioma model, that is induced by the orthotopic injection of GL261 cells into the brain (PubMed:28202361).[1] [2] [3] Publication Abstract from PubMedThe 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. 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[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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