Stradley S J, Rizo J, Bruch M D, Stroup A N, Gierasch L M
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235-9041.
Biopolymers. 1990 Jan;29(1):263-87. doi: 10.1002/bip.360290130.
Cyclic pentapeptides are excellent models for reverse turns and have been used extensively in our laboratory to explore the influence of different amino acid sequences on turn preference. This paper is divided into two parts: In the first, we review our previous studies of cyclic pentapeptides. We summarize work that demonstrates the range of conformations possible within the cyclic pentapeptide backbone, the importance of sequence chirality in determining the backbone fold, and the utility of these cyclic pentapeptides as models for various turns. In the second, we present new results on two cyclic pentapeptides that contain beta-turns with Pro-Ala or Pro-Asn sequences in the i + 1 and i + 2 positions. By stereochemical criteria, a type I beta-turn is expected to be preferred by such L-L sequences. On the other hand, in proteins Asn occurs frequently in the i + 2 position of type II turns. We asked whether the same propensity would be manifest in an isolated model peptide, and if so, what the interactions were that influenced the relative stability of the type I and type II turns. To address these questions we have compared the conformational behavior of two peptides: cyclo(Gly-Pro-Ala-D-Phe-Pro) and cyclo(D-Ala-Pro-Asn-Gly-Pro). From previous studies, we anticipated that both peptides would contain an inverse gamma-turn and a beta-turn which consisted of either Gly-Pro-Ala-D-Phe or D-Ala-Pro-Asn-Gly in positions i to i + 3, respectively. Nuclear magnetic resonance analysis confirms this overall backbone conformation. Furthermore, quantitative nuclear Overhauser effect measurements in combination with molecular dynamics simulations and torsionally-forced energy minimizations have enabled us to determine that both type I and type II beta-turns are present in equilibrium in these peptides. The introduction of Asn in position i + 2 shifts this equilibrium significantly towards type II. We have done preliminary assessment of the possible side-chain/backbone conformations that contribute to the shift in populations.
环五肽是研究β-转角的优秀模型，并且在我们实验室中被广泛用于探究不同氨基酸序列对转角偏好的影响。本文分为两个部分：第一部分，我们回顾之前对环五肽的研究。我们总结了相关工作，这些工作展示了环五肽主链内可能的构象范围、序列手性在决定主链折叠中的重要性，以及这些环五肽作为各种转角模型的实用性。第二部分，我们展示了关于两种环五肽的新结果，这两种环五肽在i + 1和i + 2位置含有Pro-Ala或Pro-Asn序列的β-转角。根据立体化学标准，这样的L-L序列预计更倾向于形成I型β-转角。另一方面，在蛋白质中，Asn经常出现在II型转角的i + 2位置。我们询问在一个孤立的模型肽中是否会表现出相同的倾向，如果是，影响I型和II型转角相对稳定性的相互作用是什么。为了解决这些问题，我们比较了两种肽的构象行为：环（Gly-Pro-Ala-D-Phe-Pro）和环（D-Ala-Pro-Asn-Gly-Pro）。根据之前的研究，我们预计这两种肽都将包含一个反向γ-转角和一个β-转角，其中β-转角分别由i到i + 3位置的Gly-Pro-Ala-D-Phe或D-Ala-Pro-Asn-Gly组成。核磁共振分析证实了这种整体主链构象。此外，定量核Overhauser效应测量结合分子动力学模拟和扭转力能量最小化，使我们能够确定这两种肽中I型和II型β-转角都以平衡状态存在。在i + 2位置引入Asn会使这种平衡显著向II型转移。我们已经对可能导致种群转移的侧链/主链构象进行了初步评估。
