Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106, Warsaw, Poland.
Chem Biodivers. 2021 Apr;18(4):e2100043. doi: 10.1002/cbdv.202100043. Epub 2021 Mar 9.
Proteins anchor copper(II) ions mainly by imidazole from histidine residues located in different positions in the primary protein structures. However, the motifs with histidine in the first three N-terminal positions (His , His , and His ) show unique Cu(II)-binding properties, such as availability from the surface of the protein, high flexibility, and high Cu(II) exchangeability with other ligands. It makes such sequences beneficial for the fast exchange of Cu(II) between ligands. Furthermore, sequences with His and His , thus, non-saturating the Cu(II) coordination sphere, are redox-active and may play a role in Cu(II) reduction to Cu(I). All human protein sequences deposited in UniProt Knowledgebase were browsed for those containing His , His , or His . Proteolytically modified sequences (with the removal of a propeptide or Met residue) were taken for the analysis. Finally, the sequences were sorted out according to the subcellular localization of the proteins to match the respective sequences with the probability of interaction with divalent copper.
蛋白质主要通过位于一级蛋白质结构中不同位置的组氨酸残基的咪唑基锚定铜（II）离子。然而，前三个 N 末端位置（His1、His2 和 His3）具有组氨酸的基序表现出独特的 Cu(II)结合特性，例如可从蛋白质表面获得、高灵活性以及与其他配体的高 Cu(II)可交换性。这使得这些序列有利于配体之间 Cu(II)的快速交换。此外，由于 His1 和 His2 未使 Cu(II)配位球饱和，因此具有氧化还原活性，并且可能在 Cu(II)还原为 Cu(I)中发挥作用。在 UniProt Knowledgebase 中浏览了所有人类蛋白质序列，以寻找包含 His1、His2 或 His3 的序列。对经过蛋白水解修饰的序列（去除前肽或 Met 残基）进行了分析。最后，根据蛋白质的亚细胞定位对序列进行了分类，以将相应的序列与二价铜相互作用的概率相匹配。
