A CONFORMATION OF CYCLOSPORINE-A IN AQUEOUS ENVIRONMENT REVEALED BY THE X-RAY STRUCTURE OF A CYCLOSPORINE-FAB COMPLEX
A CONFORMATION OF CYCLOSPORINE-A IN AQUEOUS ENVIRONMENT REVEALED BY THE X-RAY STRUCTURE OF A CYCLOSPORINE-FAB COMPLEX
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DOI：
10.1126/science.1566062
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发表时间：
1992-04-03
期刊：
影响因子：
56.9
通讯作者：
THIERRY, JC
中科院分区：
文献类型：
--
作者：
ALTSCHUH, D;VIX, O;THIERRY, JC
通过对2.65埃分辨率的结晶学分析，确定了免疫抑制药物环孢菌素A(CsA)在Fab分子络合物中的构象。CsA的这种构象类似于最近在体内观察到的与其结合蛋白--环磷酰胺酶的络合物中的构象，而与X射线和核磁共振分析所确定的分离形式的构象完全不同。由于CsA与亲环素或与Fab相互作用的表面不同，这些结果表明CsA以结合形式存在于水溶液中，而不是通过与蛋白质相互作用而产生的。
The conformation of the immunosuppressive drug cyclosporin A (CsA) in a complex with a Fab molecule has been established by crystallographic analysis to 2.65 angstrom resolution. This conformation of CsA is similar to that recently observed in the complex with the rotamase cyclophilin, its binding protein in vivo, and totally different from its conformation in an isolated form as determined from x-ray and nuclear magnetic resonance analysis. Because the surfaces of CsA interacting with cyclophilin or with the Fab are not identical, these results suggest that the conformation of CsA observed in the bound form preexists in aqueous solution and is not produced by interaction with the proteins.