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Chloride Control of the Mechanism of Human Serum Ceruloplasmin (Cp) Catalysis.

ABSTRACT: Unraveling the mechanism of ceruloplasmin (Cp) is fundamentally important toward understanding the pathogenesis of metal-mediated diseases and metal neurotoxicity. Here we report that Cl-, the most abundant anion in blood plasma, is a key component of Cp catalysis. Based on detailed spectroscopic analyses, Cl- preferentially interacts with the partially reduced trinuclear Cu cluster (TNC) in Cp under physiological conditions and shifts the electron equilibrium distribution among the two redox active type 1 (T1) Cu sites and the TNC. This shift in potential enables the intramolecular electron transfer (IET) from the T1 Cu to the native intermediate (NI) and accelerates the IET from the T1 Cu to the TNC, resulting in faster turnover in Cp catalysis.

SUBMITTER: Tian S

PROVIDER: S-EPMC6657493 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Chloride Control of the Mechanism of Human Serum Ceruloplasmin (Cp) Catalysis.

Tian Shiliang S Jones Stephen M SM Jose Anex A Solomon Edward I EI

Journal of the American Chemical Society 20190627 27

Unraveling the mechanism of ceruloplasmin (Cp) is fundamentally important toward understanding the pathogenesis of metal-mediated diseases and metal neurotoxicity. Here we report that Cl-, the most abundant anion in blood plasma, is a key component of Cp catalysis. Based on detailed spectroscopic analyses, Cl- preferentially interacts with the partially reduced trinuclear Cu cluster (TNC) in Cp under physiological conditions and shifts the electron equilibrium distribution ...[more]

PMID: 31203609

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