Davis Tara L, Walker John R, Ouyang Hui, MacKenzie Farrell, Butler-Cole Christine, Newman Elena M, Eisenmesser Elan Z, Dhe-Paganon Sirano
Structural Genomics Consortium, Banting Institute, University of Toronto, ON, Canada.
FEBS J. 2008 May;275(9):2283-95. doi: 10.1111/j.1742-4658.2008.06381.x. Epub 2008 Apr 3.
Cyclophilins comprise one of the three classes of peptidylprolyl isomerases found in all eukaryotic and prokaryotic organisms, as well as viruses. Many of the 17 annotated human cyclophilins contain the catalytic domain in tandem with other domains, and many of the specific functions of a particular cyclophilin or its associated domains remain unknown. The structure of the isomerase domain from a spliceosome-associated cyclophilin, PPWD1 (peptidylprolyl isomerase containing WD40 repeat), has been solved to 1.65 A. In the crystal, the N-terminus of one isomerase domain is bound in the active site of a neighboring isomerase molecule in a manner analogous to substrate. NMR solution studies show that this sequence binds to the active site of the cyclophilin, but cannot be turned over by the enzyme. A pseudo-substrate immediately N-terminal to the cyclophilin domain in PPWD1 could have wider implications for the function of this cyclophilin in the spliceosome, where it is located in human cells.
亲环蛋白是在所有真核生物、原核生物以及病毒中发现的三类肽基脯氨酰异构酶之一。17种已注释的人类亲环蛋白中有许多含有与其他结构域串联的催化结构域,而特定亲环蛋白或其相关结构域的许多具体功能仍不清楚。一种与剪接体相关的亲环蛋白PPWD1(含WD40重复序列的肽基脯氨酰异构酶)的异构酶结构域的结构已解析到1.65埃。在晶体中,一个异构酶结构域的N端以类似于底物的方式结合在相邻异构酶分子的活性位点上。核磁共振溶液研究表明,该序列与亲环蛋白的活性位点结合,但不能被酶催化转化。PPWD1中亲环蛋白结构域紧邻的N端假底物可能对该亲环蛋白在人类细胞中所在的剪接体中的功能有更广泛的影响。