Generation of the oxidized form protects human brain type creatine kinase against cystine-induced inactivation |
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Authors: | Li Xu-Hui Chen Zhe Gao Yan-Song Yan Yong-Bin Zhang Fang Meng Fan-Guo Zhou Hai-Meng |
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Institution: | Protein Science Laboratory of the Ministry of Education, School of Life Sciences, Tsinghua University, Beijing 100084, China. |
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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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