Scanlon M J, Norton R S
NMR Laboratory, Biomolecular Research Institute, Parkville, Australia.
Protein Sci. 1994 Jul;3(7):1121-4. doi: 10.1002/pro.5560030717.
Anthopleurin-A (AP-A) is a member of a family of sea anemone-derived polypeptides that interact with sodium channels in a voltage-dependent manner, producing a positive inotropic effect on the mammalian heart. There has been considerable interest in this molecule as a lead compound for the development of novel therapeutic agents. Earlier attempts to define the 3-dimensional structure of AP-A were complicated by the fact that it was found to exist in 2 conformations in solution. Using 1H- and 13C-NMR spectroscopy, we have now shown that this conformational heterogeneity arises from cis-trans isomerization about the Gly 40-Pro 41 peptide bond and that in the major form of the protein this peptide bond adopts a cis conformation. Furthermore, the increased sensitivity afforded by higher-field NMR has allowed identification of additional minor conformations of AP-A, the origin of which is presently unknown. We believe there will be many more examples of the detection by high-field NMR of previously unobserved minor conformations of proteins in solution.
海葵素 -A（AP -A）是一类源自海葵的多肽家族成员，它以电压依赖的方式与钠通道相互作用，对哺乳动物心脏产生正性肌力作用。作为开发新型治疗药物的先导化合物，该分子一直备受关注。早期确定AP -A三维结构的尝试因发现其在溶液中以两种构象存在而变得复杂。利用1H-和13C-核磁共振光谱，我们现已表明这种构象异质性源于围绕甘氨酸40 - 脯氨酸41肽键的顺反异构化，并且在蛋白质的主要形式中，该肽键采用顺式构象。此外，更高场强核磁共振提供的更高灵敏度使得能够识别AP -A的其他次要构象，其起源目前尚不清楚。我们相信，通过高场核磁共振检测溶液中蛋白质以前未观察到的次要构象将会有更多实例。
