Reimer Ulf, Fischer Gunter
Institut für Organische Chemie, AK Griesinger, Universität Frankfurt, Frankfurt/Main, Germany.
Biophys Chem. 2002 May 2;96(2-3):203-12. doi: 10.1016/s0301-4622(02)00013-3.
Peptidyl-prolyl cis/trans isomerization, observed in the native state of an increasing number of proteins, is of considerable biological significance. The first evidence for an asymmetric transmission along the polypeptide chain of the structural effects of prolyl isomerization is now derived from the statistics of the C(alpha)/C(alpha)-atom distance distributions in the crystal structures of 848 non-homologous proteins. More detailed information on how isomerization affects segments adjacent to proline is obtained from crystal structures of proteins, that are more than 95% homologous, and that exhibit two different states of isomerization at a particular prolyl bond. The resulting 64 cases, which represent 3.8% of the database used, form pairs of coordinates which were analyzed for the existence of isomer-specific intramolecular nonbonded C(alpha)/C(alpha)-atom distances around the critical proline, and for the positional preferences for particular amino acids in the isomeric sequence segment. The probability that a native protein exhibits both prolyl isomers in the crystalline state increases in particular with a Pro at the third position N-terminal to the isomeric bond (-3 position), and with Ser, Gly and Asp at the position preceding the isomeric bond (-1 position). Structural alignment of matched pairs of isomeric proteins generates three classes with respect to position-specific distribution of C(alpha)-atom displacements around an isomeric proline imide bond. In the majority of cases the distribution of these intermolecular isomer-specific C(alpha)-atom distances shows a symmetric behavior for the N-terminal and C-terminal segment flanking the proline residue, and the magnitude did not exceed 1.3+/-0.6 A including the C(alpha) atoms in proximity to the prolyl bond. However, in the remaining 12 protein pairs the structural changes are unidirectional relative to the isomerizing bond whereby the magnitude of the isomer-specific effect exceeds 3.0+/-2.0 A even at positions remote to proline. Interestingly, the magnitude of the intramolecular isomer-specific C(alpha) atom displacements reveals a lever-arm amplification of the isomerization-mediated structural changes in a protein backbone. The observed backbone effects provide a structural basis for isomer-specific reactions of proline-containing polypeptides, and thus may play a role in biological recognition and regulation.
在越来越多的蛋白质天然状态中观察到的肽基 - 脯氨酰顺反异构化具有相当重要的生物学意义。脯氨酰异构化结构效应沿多肽链的不对称传递的首个证据，现在来自于848种非同源蛋白质晶体结构中Cα/Cα原子距离分布的统计数据。关于异构化如何影响脯氨酸相邻片段的更详细信息，是从同源性超过95%且在特定脯氨酰键处呈现两种不同异构化状态的蛋白质晶体结构中获得的。由此得到的64个案例，占所用数据库的3.8%，形成了坐标对，对其进行了分析，以确定关键脯氨酸周围是否存在异构体特异性分子内非键合Cα/Cα原子距离，以及异构体序列片段中特定氨基酸的位置偏好。天然蛋白质在晶体状态下同时呈现两种脯氨酰异构体的概率，尤其在异构体键N端第三个位置（-3位置）为脯氨酸，以及异构体键前一个位置（-1位置）为丝氨酸、甘氨酸和天冬氨酸时会增加。异构化蛋白质匹配对的结构比对，就围绕异构化脯氨酰亚胺键的Cα原子位移的位置特异性分布产生了三类情况。在大多数情况下，这些分子间异构体特异性Cα原子距离的分布，对于脯氨酸残基两侧的N端和C端片段呈现对称行为，并且其大小不超过1.3±0.6 Å，包括靠近脯氨酰键的Cα原子。然而，在其余12对蛋白质中，结构变化相对于异构化键是单向的，即使在远离脯氨酸的位置，异构体特异性效应的大小也超过3.0±2.0 Å。有趣的是，分子内异构体特异性Cα原子位移的大小揭示了蛋白质主链中异构化介导的结构变化的杠杆臂放大效应。观察到的主链效应为含脯氨酸多肽的异构体特异性反应提供了结构基础，因此可能在生物识别和调节中发挥作用。
