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Solution structure of the calcium channel antagonist ω‐conotoxin GVIA
Author(s) -
Skalicky Jack J.,
Ciesla D. Joseph,
Pardi Arthur,
Metzler William J.,
Galdes Alphonse
Publication year - 1993
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560021005
Subject(s) - antiparallel (mathematics) , peptide , chemistry , calcium channel , peptide sequence , crystallography , biophysics , dihedral angle , stereochemistry , hydrogen bond , calcium , biochemistry , molecule , physics , biology , organic chemistry , quantum mechanics , magnetic field , gene
Abstract The three‐dimensional solution structure is reported for ω‐conotoxin GVIA, which is a potent inhibitor of presynaptic calcium channels in vertebrate neuromuscular junctions. Structures were generated by a hybrid distance geometry and restrained molecular dynamics approach using interproton distance, torsion angle, and hydrogen‐bonding constraints derived from 1 H NMR data. Conformations of GVIA with low constraint violations converged to a common peptide fold. The secondary structure in the peptide is an antiparallel triple‐stranded β‐sheet containing a β‐hairpin and three tight turns. The NMR data are consistent with the region of the peptide from residues S9 to C16 being more dynamic than the rest of the peptide. The peptide has an amphiphilic structure with a positively charged hydrophilic side and an opposite side that contains a small hydrophobic region. Residues that are thought to be important in binding and function are located on the hydrophilic face of the peptide.