Crystal structure implies that cyclophilin predominantly catalyzes the trans to cis isomerization.
Crystal structure implies that cyclophilin predominantly catalyzes the trans to cis isomerization.
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晶体结构表明亲环蛋白主要催化反式异构化为顺式异构化。
DOI：
10.1021/bi9602775
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Ke,H
中科院分区：
文献类型：
--
作者：
Zhao,Y;Ke,H
本文测定了人重组亲环素A与琥珀酰-Ala-Ala-Pro-Phe-对硝基苯胺（AAPF）底物复合物的晶体结构，并在2.4 μ m分辨率下精确到R因子0.189。该结构仅揭示了与亲环素A以1：1的化学计量结合的底物的异构体。该结合率不同于亲环素A与四肽N-乙酰基-Ala-Ala-Pro-Ala-酰胺甲基香豆素复合的结构。模型对接表明AAPF的转化不适合活性位点。只有AAPF的异构体与亲环素A结合，这表明亲环素A主要催化肽基-脯氨酰胺键的转座异构化。基于该结构，有人提出Arg 55与氮形成氢键，解除脯氨酰胺键的共振，从而促进顺反旋转。
The crystal structure of human recombinant cyclophilin A complexed with a substrate of succinyl-Ala-Ala-Pro-Phe-p-nitroanilide (AAPF) has been determined and refined to anR-factor of 0.189 at 2.4 Å resolution. The structure revealed only thecisform of the substrate bound to cyclophilin A in a stoichiometry of 1:1. This binding ratio is different from the structure of cyclophilin A complexed with the tetrapeptideN-acetyl-Ala-Ala-Pro-Ala-amidomethylcourmarin. Model docking revealed that thetransform of AAPF does not fit into the active site. The observation that only thecisform of AAPF binds to cyclophilin A implies that cyclophilin A predominantly catalyzes thetranstocisisomerization of a peptidyl-prolyl amide bond. On the basis of the structure, it is proposed that Arg55 hydrogen-bonds to the nitrogen to deconjugate the resonance of the prolyl amide bond and thus facilitates thecis−transrotation.