Solution structure determination by two-dimensional H-1 NMR of omega-conotoxin MVIID, a calcium channel blocker peptide

The three-dimensional structure of omega-conotoxin MVIID has been determine d in aqueous solution by two-dimensional H-1 NMR techniques. A total of 267 relevant upper-bound distance restraints were used to obtain a family of c onvergent structures using molecular dynamics methods. A standard simulated annealing protocol using the XPLOR program included in ARIA provided a tot al of 18 final structures. The averaged RMSD between these structures and t he mean atomic coordinates was 0.8 +/- 0.3 A for the backbone atoms. The hi ghest mobility was observed in the segments between residues 10 to 13, comp rising Tyr 13, one of the residues shown to be important for binding of ome ga-conotoxin GVIA and MVIIA to N-type calcium channels. The three-dimension al structure is stabilised by the three disulfide bonds and includes a shor t antiparallel beta-strand between residues 5-8, 23-25 and 19-21. The foldi ng for this non-N-type calcium channel blocker is similar to that previousl y calculated for omega-conotoxins GVIA MVIIA and MWC. This suggests the dis ulfide bond pattern fixes the structure. The reported three-dimensional inf ormation can. be used to advantage in order to highlight the, structural pa rameters involved in discrimination among calcium channel subtypes. (C) 199 9 Academic Press.