Kinetics of Zn²⁺-induced Brain Type Creatine Kinase Unfolding and Aggregation
2010
Mu, Hang | Lü, Zhi-Rong | Park, Daeui | Kim, Byoung-Chul | Bhak, Jong | Zou, Fei | Yang, Jun-Mo | Li, Sen | Park, Yong-Doo | Zou, He-Chang | Zhou, Hai-Meng
We studied the effect of Zn²⁺ on the folding and aggregation of brain creatine kinase (CK-BB). We developed a method to purify CK-BB from rabbit brain and conducted inhibition kinetics and unfolding studies of CK-BB. Zn²⁺ conspicuously aggregated and osmolytes, such as glycine and proline, were able to suppress the formation of aggregates and protect the enzymatic activity against Zn²⁺. These results suggest that Zn²⁺ might act as a risk factor for CK-BB in the brain under certain conditions, and some osmolytes may help CK-BB to sustain the active state when Zn²⁺ is present. Our study provides useful information regarding the effect of Zn²⁺ on brain-derived metabolic enzymes, especially those that are putatively related to brain disease. Furthermore, our study suggests that although Zn²⁺ may induce CK-BB inactivation and misfolding, the ability of some abundant proteins and osmolytes to chelate Zn²⁺ nonspecifically may protect CK-BB and allow it to exist in the active form.
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