SOLUTION STRUCTURES OF ALPHA-CONOTOXIN-G1 DETERMINED BY TWO-DIMENSIONAL NMR-SPECTROSCOPY
SOLUTION STRUCTURES OF ALPHA-CONOTOXIN-G1 DETERMINED BY TWO-DIMENSIONAL NMR-SPECTROSCOPY
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DOI：
10.1021/bi00439a026
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发表时间：
1989-06-27
期刊：
影响因子：
2.9
通讯作者：
MANICONTE, D
中科院分区：
文献类型：
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作者：
PARDI, A;GALDES, A;MANICONTE, D
二维核磁共振数据已被用来生成α-芋螺毒素G1的溶液结构，该毒素是乙酰胆碱受体的一种有效的肽拮抗剂。结构信息以质子-质子核间距离约束的形式获得，初始结构由距离几何算法生成。通过使用距离几何测量结构作为约束能量最小化程序的输入，产生了能量上更有利的结构。这两种计算的结果都表明，核磁共振数据很好地定义了分子的整体主链构象，而侧链构象通常不太清楚。从核磁共振数据得到的主要结构特征是以PRO5和Arg9残基为中心的紧密转弯。将这些溶液结构与以前提出的芋螺毒素G1模型进行比较，并结合化学修饰研究和其他乙酰胆碱受体拮抗剂的结构性质对核磁共振数据进行解释，以深入了解这些多肽毒素中的构效关系。
Two-dimensional NMR data have been used to generate solution structures of .alpha.-conotoxin G1, a potent peptide antagonist of the acetylcholine receptor. Structural information was obtained in the form of proton-proton internuclear distance constraints, and initial structures were produced with a distance geometry algorithm. Energetically more favorable structures were generated by using the distance geomoetry structures as input for a constrained energy minimization program. The results of both of these calculations indicate that the overall backbone conformation of the molecule is well-defined by the NMR data whereas the side-chain conformations are generally less well-defined. The main structural features derived from the NMR data were the presence of tight turns centered on residues Pro5 and Arg9. The solution structures are compared with previous proposed models of conotoxin G1, and the NMR data are interpreted in conjunction with chemical modification studies and structural properties of other antagonists of the acetylcholine receptor to gain insight into structure-activity relationships in these peptide toxins.