Generation of the oxidized form protects human brain type creatine kinase against cystine-induced inactivation
2011
Abstract Cystine accumulation in cystinotic patients has been reported to inhibit brain type creatine kinase (BBCK), an important thiol-containing enzyme in energy homeostasis. In this research, we found that the oxidized form of BBCK (O-BBCK) was induced by cystine, and the intramolecular disulfide bond of O-BBCK was formed between Cys74 and Cys254. The wild type BBCK was found to be more resistant to the inactivation induced by cystine when compared to the single point mutant C74S or C254S. Meanwhile, the existence of GSH could protect the wild type BBCK more efficiently than the mutants. These observations suggested that the ability to generate the oxidized form could protect BBCK against the intracellular oxidative stress.
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