Fischer G, Wittmann-Liebold B, Lang K, Kiefhaber T, Schmid F X
WB Biochemie, Sektion Biowissenschaften, Martin-Luther-Universität Halle, GDR.
Nature. 1989 Feb 2;337(6206):476-8. doi: 10.1038/337476a0.
The enzyme peptidyl-prolyl cis-trans isomerase (PPIase) was recently discovered in mammalian tissues and purified from porcine kidney. It catalyses the slow cis-trans isomerization of proline peptide (Xaa-Pro) bonds in oligopeptides and accelerates slow, rate-limiting steps in the folding of several proteins. Here, we report the N-terminal sequence of PPIase together with further chemical and enzymatic properties. The results indicate that this enzyme is probably identical to cyclophilin, a recently discovered mammalian protein which binds tightly to cyclosporin A (CsA). Cyclophilin is thought to be linked to the immunosuppressive action of CsA. The first 38 amino-acid residues of porcine PPIase and of bovine cyclophilin are identical and the two proteins both have a relative molecular mass of about 17,000 (ref. 7). The catalysis of prolyl isomerization in oligopeptides and of protein folding by PPIase are strongly inhibited in the presence of low levels of CsA. The activities of both PPIase and cyclophilin depend on a single sulphydryl group. At present it is unknown whether the inhibition of prolyl isomerase activity is related with the immunosuppressive action of CsA.
肽基脯氨酰顺反异构酶（PPIase）最近在哺乳动物组织中被发现，并从猪肾中纯化出来。它催化寡肽中脯氨酸肽键（Xaa-Pro）缓慢的顺反异构化反应，并加速几种蛋白质折叠过程中的缓慢限速步骤。在此，我们报告PPIase的N端序列以及进一步的化学和酶学性质。结果表明，这种酶可能与亲环蛋白相同，亲环蛋白是最近发现的一种与环孢菌素A（CsA）紧密结合的哺乳动物蛋白。亲环蛋白被认为与CsA的免疫抑制作用有关。猪PPIase和牛亲环蛋白的前38个氨基酸残基相同，且这两种蛋白质的相对分子质量均约为17000（参考文献7）。在低水平CsA存在的情况下，PPIase对寡肽中脯氨酰异构化反应的催化作用以及对蛋白质折叠的催化作用均受到强烈抑制。PPIase和亲环蛋白的活性均依赖于一个巯基。目前尚不清楚脯氨酰异构酶活性的抑制是否与CsA的免疫抑制作用有关。
