Howard Bruce R, Vajdos Felix F, Li Su, Sundquist Wesley I, Hill Christopher P
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA.
Nat Struct Biol. 2003 Jun;10(6):475-81. doi: 10.1038/nsb927.
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 sp3 hybridization of the proline nitrogen in the transition state.
亲环蛋白构成了一个普遍存在的蛋白质家族，其功能包括蛋白质折叠、转运和信号传导。它们同时具有序列特异性结合和脯氨酸顺反异构酶活性，亲环蛋白A（CypA）与HIV-1 CA蛋白之间的相互作用就是例证。在此，我们报道了CypA与HIV-1 CA蛋白变体形成复合物的晶体结构，这些变体优先与顺式或反式构象的底物脯氨酸残基结合。顺式和反式脯氨酸底物通过其N端残基的重排被容纳在酶活性位点内，且主链路径的扭曲最小。CypA的精氨酸55胍基可能通过锚定底物脯氨酸氧并稳定过渡态下脯氨酸氮的sp3杂化来促进催化作用。
