Institute of Biochemistry and Biophysics, Polish Academy of Science, Pawińskiego 5a, 02-106 Warsaw, Poland.
Dalton Trans. 2021 Dec 20;51(1):14-26. doi: 10.1039/d1dt02878b.
Cu(II)-peptide complexes are intensely studied as models for biological peptides and proteins and for their direct importance in copper homeostasis and dyshomeostasis in human diseases. In particular, high-affinity ATCUN/NTS (amino-terminal copper and nickel/N-terminal site) motifs present in proteins and peptides are considered as Cu(II) transport agents for copper delivery to cells. The information on the affinities and structures of such complexes derived from steady-state methods appears to be insufficient to resolve the mechanisms of copper trafficking, while kinetic studies have recently shown promise in explaining them. Stopped-flow experiments of Cu(II) complexation to ATCUN/NTS peptides revealed the presence of reaction steps with rates much slower than the diffusion limit due to the formation of novel intermediate species. Herein, the state of the field in Cu(II)-peptide kinetics is reviewed in the context of physiological data, leading to novel ideas in copper biology, together with the discussion of current methodological issues.
Cu(II)-肽配合物作为生物肽和蛋白质的模型受到了广泛的研究，因为它们在铜的体内平衡和人体疾病中的失调方面具有直接的重要性。特别是，存在于蛋白质和肽中的高亲和力 ATCUN/NTS（氨基端铜和镍/N 端位点）基序被认为是铜向细胞输送的 Cu(II)转运剂。从稳态方法获得的关于这些配合物的亲和力和结构的信息似乎不足以解析铜运输的机制，而动力学研究最近显示出了解释这些机制的希望。Cu(II)与 ATCUN/NTS 肽的配位的停流实验揭示了由于新的中间物种的形成，反应步骤的速率比扩散限制慢得多，这些步骤的速率比扩散限制慢得多。本文在生理数据的背景下综述了 Cu(II)-肽动力学的研究现状，为铜生物学提出了新的观点，并讨论了当前的方法学问题。
