Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw 02-106, Poland.
Department of Medicine (Royal Melbourne Hospital), The University of Melbourne, Melbourne, Victoria 3010, Australia.
Inorg Chem. 2021 Nov 15;60(22):16927-16931. doi: 10.1021/acs.inorgchem.1c03084. Epub 2021 Nov 3.
Human serum albumin (HSA) and the growth factor glycyl-l-histidyl-l-lysine (GHK) bind Cu as part of their normal functions. GHK is found at its highest concentration in the albumin-rich fraction of plasma, leading to speculation that HSA and GHK form a ternary Cu complex. Although preliminary evidence was presented 40 years ago, the structure and stability of such a complex have remained elusive. Here, we show that two ternary Cu(GHK)N complexes are formed between GHK and the imino nitrogen (N) of His side chains of HSA. We identified His3 as one site of ternary complex formation (conditional binding constant = 2900 M at pH 7.4), with the second site ( = 1700 M) likely being supplied by either His128 or His510. Together with the established role of HSA as a molecular shuttle in the blood, these complexes may aid the transport of the exchangeable Cu pool and the functional form of GHK.
人血清白蛋白 (HSA) 和生长因子甘氨酰-L-组氨酰-L-赖氨酸 (GHK) 作为其正常功能的一部分结合 Cu。GHK 在富含白蛋白的血浆部分达到最高浓度，这导致人们推测 HSA 和 GHK 形成三元 Cu 配合物。尽管 40 年前提出了初步证据，但该配合物的结构和稳定性仍然难以捉摸。在这里，我们表明 GHK 和 HSA 的 His 侧链的亚氨基氮 (N) 之间形成了两种三元 Cu(GHK)N 配合物。我们确定 His3 是三元配合物形成的一个位点（在 pH 7.4 时的条件结合常数 = 2900 M），第二个位点（ = 1700 M）可能由 His128 或 His510 提供。结合 HSA 在血液中作为分子穿梭的既定作用，这些配合物可能有助于可交换 Cu 池和 GHK 的功能形式的运输。
