Sendzik Madison, Pushie M Jake, Stefaniak Ewelina, Haas Kathryn L
Department of Chemistry and Physics, Saint Mary's College , Notre Dame, Indiana 46556, United States.
Department of Surgery, University of Saskatchewan , Saskatoon, Saskatchewan S7N 5E5, Canada.
Inorg Chem. 2017 Dec 18;56(24):15057-15065. doi: 10.1021/acs.inorgchem.7b02397. Epub 2017 Nov 22.
Human serum albumin (HSA) is a major Cu carrier in human blood and in cerebrospinal fluid. A major assumption is that Cu bound to HSA is in the Cu(II) oxidation state; thus, interactions between HSA and Cu(II) have been intensely investigated for over four decades. HSA has been reported previously to support the reduction of Cu(II) to the Cu(I) oxidation state in the presence of the weak reductant, ascorbate; however, the interactions between HSA and Cu(I) have not been explicitly investigated. Here, we characterize both the apparent affinity of HSA for Cu(I) using solution competition experiments and the coordination structure of Cu(I) bound to HSA using X-ray absorption spectroscopy and in silico modeling. We find that HSA binds to Cu(I) at pH 7.4 with an apparent conditional affinity of K = 10 using digonal coordination in a structure that is similar to the bis-His coordination modes characterized for amyloid beta (Aβ) and the prion protein. This high affinity and familiar Cu(I) coordination structure suggests that Cu(I) interaction with HSA in human extracellular fluids is unappreciated in the current scientific literature.
人血清白蛋白（HSA）是人体血液和脑脊液中的主要铜载体。一个主要假设是，与HSA结合的铜处于Cu（II）氧化态；因此，在过去四十多年里，人们对HSA与Cu（II）之间的相互作用进行了深入研究。此前有报道称，在弱还原剂抗坏血酸存在的情况下，HSA能支持将Cu（II）还原为Cu（I）氧化态；然而，HSA与Cu（I）之间的相互作用尚未得到明确研究。在此，我们通过溶液竞争实验表征了HSA对Cu（I）的表观亲和力，并利用X射线吸收光谱和计算机模拟确定了与HSA结合的Cu（I）的配位结构。我们发现，在pH 7.4时，HSA通过双角配位与Cu（I）结合，其表观条件亲和力K = 10，该结构类似于淀粉样β蛋白（Aβ）和朊病毒蛋白的双组氨酸配位模式。这种高亲和力和熟悉的Cu（I）配位结构表明，目前科学文献中尚未认识到人体细胞外液中Cu（I）与HSA的相互作用。
