Structure of recombinant human cyclophilin J, a novel member of the cyclophilin family
Structure of recombinant human cyclophilin J, a novel member of the cyclophilin family
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DOI：
10.1107/s0907444904033189
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发表时间：
2005-03-01
影响因子：
2.2
通讯作者：
Xia, ZX
中科院分区：
文献类型：
--
作者：
Huang, LL;Zhao, XM;Xia, ZX
亲环蛋白 (CyP) 是一大类高度保守、普遍存在的肽基-脯氨酰顺反异构酶。 CyP 还被确定为免疫抑制药物环孢菌素 A 的特异性受体，并参与多种生物学功能。 CyPJ 是 CyP 家族的新成员，人 CyPJ (hCyPJ) 是由人胎儿脑中的亲环蛋白样基因编码的蛋白质，与人亲环蛋白 A (hCyPA) 具有 50% 的序列同一性。重组hCyPJ在大肠杆菌中表达并纯化。 hCyPJ 的三维结构已通过使用 hCyPA 结构作为搜索模型的分子置换确定，并以 2.6 埃分辨率进行了细化。 hCyPJ 分子包含 4 个螺旋和 1 个由 8 条反向平行 β 链组成的 β 桶。 hCyPJ 的总体二级和三级结构与 hCyPA 相似，但 hCyPJ 包含一个额外的二硫键和四个构象与 hCyPA 显着不同的片段。根据与 hCyPA 的序列比对，预计 hCyPJ 的 His43 和 Gln52 是活性位点。 hCyPJ 结构显示出接近 His43 和 Gln52 的保守水分子，这似乎支持溶剂辅助机制。
Cyclophilins (CyPs) are a large class of highly conserved ubiquitous peptidyl-prolyl cis-trans isomerases. CyPs have also been identified as being a specific receptor for the immunosuppressive drug cyclosporin A and are involved in a variety of biological functions. CyPJ is a novel member of the CyP family and human CyPJ (hCyPJ) is the protein encoded by a cyclophilin-like gene from human foetal brain, which shows 50% sequence identity to human cyclophilin A (hCyPA). Recombinant hCyPJ was expressed in Escherichia coli and purified. The three-dimensional structure of hCyPJ has been determined by molecular replacement using the hCyPA structure as the search model and has been refined at 2.6 Angstrom resolution. The hCyPJ molecule contains four helices and one beta-barrel composed of eight antiparallel beta-strands. The overall secondary and tertiary structures of hCyPJ are similar to those of hCyPA, but hCyPJ contains an additional disulfide bridge and four segments with conformations that are strikingly different from those of hCyPA. His43 and Gln52 of hCyPJ are expected to be the active sites based on sequence alignment with hCyPA. The hCyPJ structure shows a conserved water molecule close to His43 and Gln52 which appears to support the solvent-assisted mechanism.