Sevilla P, Bruix M, Santoro J, Gago F, García A G, Rico M
Dpto. Química Físca II, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
Biochem Biophys Res Commun. 1993 May 14;192(3):1238-44. doi: 10.1006/bbrc.1993.1549.
omega-Conotoxin GVIA, a peptide of 27 amino acid residues and three disulfide bridges, has been studied by NMR techniques. The complete assignment of the corresponding proton NMR spectra was performed by two-dimensional sequence specific methods at 288 K and pH 3.5. On the basis of 169 distance restraints derived from this analysis, the three-dimensional structure was obtained. A total of 30 initial structures were generated by distance geometry methods and further refined by restrained energy minimization techniques yielding a final set of 8 structures. The mean root-mean-square deviation between each of the 8 structures and the mean atomic coordinates for all residues is 0.82 +/- 0.06 A for the backbone atoms and 1.45 +/- 0.18 A for all non-H atoms. The structure shows a globular folding pattern that is stabilized by the three disulfide linkages and a number of intramolecular hydrogen bonds. A total of 14 hydroxyl groups are found at the periphery fully exposed to the solvent. These groups, together with the charged side chains of Lys and Arg residues emerging radially from the peptide core, provide specific recognition elements for the interaction of this toxin with neuronal calcium channels.
ω-芋螺毒素GVIA是一种含有27个氨基酸残基和三个二硫键的肽，已通过核磁共振技术进行了研究。在288K和pH 3.5条件下，采用二维序列特异性方法对相应的质子核磁共振谱进行了完全归属。基于该分析得出的169个距离约束条件，获得了三维结构。通过距离几何方法总共生成了30个初始结构，并通过约束能量最小化技术进一步优化，得到了最终的8个结构。这8个结构中每个结构与所有残基的平均原子坐标之间，主链原子的平均均方根偏差为0.82±0.06 Å，所有非氢原子的平均均方根偏差为1.45±0.18 Å。该结构呈现出一种球状折叠模式，由三个二硫键和许多分子内氢键稳定。在肽的外围总共发现了14个完全暴露于溶剂的羟基。这些基团，连同从肽核心径向伸出的赖氨酸和精氨酸残基的带电侧链，为该毒素与神经元钙通道的相互作用提供了特定的识别元件。
