含铜/镍金属酶的成熟需要一系列的铜/镍金属伴侣蛋白,这些铜/镍金属伴侣蛋白分别参与铜或者镍的转运,对维持细胞体内铜/镍金属平衡至关重要,同时金属酶完成金属催化活性中心的组装也依赖于这类伴侣蛋白。近年来关于铜/镍金属蛋白的研究取得可喜的进展,这些研究为进一步认识体内铜/镍平衡体系提供了重要依据。本文首先简要地介绍铜的摄取和细胞内平衡体系,接着着重介绍三个重要的铜转运蛋白Atoxl、Coxl7和CCS关于结构和功能的进展,以及这些铜转运蛋白和药物相互作用的机理。然后详细介绍在氢化酶和脲酶成熟路径中参与了镍的摄取、调节、转运和存储,维持细胞内镍金属平衡的镍伴侣蛋白,并介绍了脲酶、氢化酶这两条成熟路径之间的联系。
Maturation of copper- and nickel-containing enzymes relies on a battery of metallochaperones, which play an important role in the transport and trafficking of Cu or Ni, and assist the assembly of metallocenter in metalloenzymes. Significant progress on the structure and function of metallochaperones has been made in the past years, improving our understanding on the homeostasis of Cu/Ni in cells. Recent progress of Cu/Ni chaperones is summarized in this review. The blueprint of Cu import and homeostasis is briefly discussed followed by the structural and functional aspects of selected Cu chaperones, i.e. Atoxl, Coxl7 and CCS. Moreover, the putative relationships between Cu chaperones and drugs are discussed. The second part focuses on the maturation of hydrogenase and urease, in which a series of Ni chaperones interacts with each other to achieve the homeostasis of nickel. Selected structural complexes and in vivo functional study of the chaperones are emphasized, the "cross- talk" between the two maturation pathways is presented.