An Insight into the Mechanism of Human Cysteine Dioxygenase KEY ROLES OF THE THIOETHER-BONDED TYROSINE-CYSTEINE COFACTOR

摘要: Cysteine dioxygenase is a non-heme mononuclear iron metalloenzyme that catalyzes the oxidation of cysteine to sulfinic acid with addition molecular dioxygen. This irreversible oxidative catabolism initiates several important metabolic pathways related diverse sulfurate compounds. therefore very for maintaining proper hepatic concentration intracellular free cysteine. Mechanisms mouse and rat dioxygenases have recently been reported based on their crystal structures in absence substrates, although there still lack direct evidence. Here we report first structure human complex its substrate L-cysteine 2.7A, together enzymatic activity metal content assays single point mutants. Our results provide an insight into new mechanism thiol dioxygenation catalyzed by dioxygenase, which tightly associated thioether-bonded tyrosine-cysteine cofactor involving Tyr-157 Cys-93. cross-linked protein-derived plays key roles different from those galactose oxidase. provides potential target therapy diseases including neurodegenerative autoimmune diseases.