Structure and Affinity of Cu(I) Bound to Human Serum Albumin.

Journal Article (Journal Article)

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 KCu(I):HSA = 1014.0 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.

Full Text

Duke Authors

Cited Authors

  • Sendzik, M; Pushie, MJ; Stefaniak, E; Haas, KL

Published Date

  • December 2017

Published In

Volume / Issue

  • 56 / 24

Start / End Page

  • 15057 - 15065

PubMed ID

  • 29166002

Electronic International Standard Serial Number (EISSN)

  • 1520-510X

International Standard Serial Number (ISSN)

  • 0020-1669

Digital Object Identifier (DOI)

  • 10.1021/acs.inorgchem.7b02397


  • eng