去七肽（B24 - B30）胰岛素的晶体结构，分辨率为1.6埃：对受体结合的影响
Crystal structure of desheptapeptide(B24-B30)insulin at 1.6 A resolution: implications for receptor binding.
作者信息
Bao S J, Xie D L, Zhang J P, Chang W R, Liang D C
机构信息
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing.
出版信息
Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):2975-80. doi: 10.1073/pnas.94.7.2975.
Abstract
The crystal structure of desheptapeptide (B24-B30) insulin (DHPI), a virtually inactive analog of insulin, was determined at 1.6 A resolution. In the refined structure model, DHPI retains three alpha-helices (A1-A8, A12-A18, and B9-B19) as its structural framework, while great conformational changes occur in the N and C termini of B-chain. The beta-turn, which lies in B20-B30 in insulin and insulin analogs with high potency, no longer exists in DHPI. Relative motion is observed among the three alpha-helices, each as a rigid functional group. In contrast, a region covering B5-B6 and A6-A11 exhibits a relatively stable conformation. We interpret our results as identifying: (i) the importance of beta-turn in determining the receptor-binding potency of insulin and (ii) a leading role of PheB24 in maintaining the beta-turn structure.
摘要
去七肽（B24 - B30）胰岛素（DHPI）是一种几乎没有活性的胰岛素类似物，其晶体结构在1.6埃分辨率下得以确定。在优化后的结构模型中，DHPI保留了三个α - 螺旋（A1 - A8、A12 - A18和B9 - B19）作为其结构框架，而B链的N端和C端则发生了巨大的构象变化。在胰岛素及高效胰岛素类似物中位于B20 - B30的β - 转角在DHPI中不再存在。三个α - 螺旋各自作为一个刚性功能基团之间存在相对运动。相比之下，覆盖B5 - B6和A6 - A11的区域呈现出相对稳定的构象。我们将研究结果解读为：（i）β - 转角在决定胰岛素受体结合效力方面的重要性；（ii）苯丙氨酸B24在维持β - 转角结构中起主导作用。
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