Structural insights into the catalytic mechanism of cyclophilin A
Structural insights into the catalytic mechanism of cyclophilin A
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DOI：
10.1038/nsb927
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发表时间：
2003-06-01
期刊：
影响因子：
--
通讯作者：
Hill, CP
中科院分区：
文献类型：
--
作者：
Howard, BR;Vajdos, FF;Hill, CP
亲环素是一个广泛存在的蛋白质家族，其功能包括蛋白质折叠、转运和信号转导。它们具有序列特异性结合和脯氨酸顺反异构酶活性，如亲环素A（CypA）和HIV-1 CA蛋白之间的相互作用所例示。在这里，我们报告的晶体结构CypA在复杂的HIV-1 CA蛋白的变体，优先结合与底物脯氨酸残基的顺式或反式构象。顺式-和反式- Pro底物通过其N-末端残基的重排被容纳在酶活性位点内，并且在主链的路径中具有最小的扭曲。CypA Arg 55胍基可能通过锚定底物脯氨酸氧和稳定过渡态脯氨酸氮的sp（3）杂化来促进催化。
Cyclophilins constitute a ubiquitous protein family whose functions include protein folding, transport and signaling. They possess both sequence-specific binding and proline cis-trans isomerase activities, as exemplified by the interaction between cyclophilin A ( CypA) and the HIV-1 CA protein. Here, we report crystal structures of CypA in complex with HIV-1 CA protein variants that bind preferentially with the substrate proline residue in either the cis or the trans conformation. Cis - and trans - Pro substrates are accommodated within the enzyme active site by rearrangement of their N-terminal residues and with minimal distortions in the path of the main chain. CypA Arg55 guanidinium group probably facilitates catalysis by anchoring the substrate proline oxygen and stabilizing sp(3) hybridization of the proline nitrogen in the transition state.