Targeted removal of the FA2 site on human albumin prevents fatty acid-mediated inhibition of Zn²⁺ binding.

ABSTRACT: Zinc is required for virtually all biological processes. In plasma, Zn²⁺ is predominantly transported by human serum albumin (HSA), which possesses two Zn²⁺-binding sites of differing affinities (sites A and B). Fatty acids (FAs) are also transported by HSA, with seven structurally characterized FA-binding sites (named FA1-FA7) known. FA binding inhibits Zn²⁺-HSA interactions, in a manner that can impact upon hemostasis and cellular zinc uptake, but the degree to which binding at specific FA sites contributes to this inhibition is unclear. Wild-type HSA and H9A, H67A, H247A, and Y150F/R257A/S287A (FA2-KO) mutant albumins were expressed in Pichia pastoris. Isothermal titration calorimetry studies revealed that the Zn²⁺-binding capacity at the high

SUBMITTER: Wu D 

PROVIDER: S-EPMC11179626 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature