Role of a Tyrosine Radical in Human Ceruloplasmin Catalysis.

ABSTRACT: Multicopper oxidases (MCOs) are a large family of diverse enzymes found in both eukaryotes and prokaryotes that couple one-electron oxidations of various substrates to the four-electron reduction of O₂ to H₂O, functioning through a set of metallocofactors consisting of one type 1 copper (T1 Cu) and one trinuclear copper cluster (TNC). Human serum ceruloplasmin (Cp) is a unique member of MCOs composed of six cupredoxin domains and harbors six Cu ions arranged as three T1 Cu and one TNC. The native substrate of Cp is Fe²⁺. It is an essential ferroxidase critical for iron homeostasis and is closely associated with metal-mediated diseases and metal neurotoxicity. In human serum, Cp operates under substrate-limiting low [Fe²⁺] but high [O₂]

SUBMITTER: Tian S 

PROVIDER: S-EPMC7596862 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature