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Kinetics of Zn2+-induced Brain Type Creatine Kinase Unfolding and Aggregation

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Abstract

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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Abbreviations

CK-BB:

homodimer brain-type of creatine kinase

ANS:

1-anilinonaphthalene-8-sulfonate

CD:

circular dichroism

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Acknowledgments

Dr. Fei Zou was supported by a grant from the National Basic Research Program of China (no. 2006CB504100). Dr. Jong Bhak was supported by a grant from the KRIBB Research Initiative Program of Korea. Dr. Yong-Doo Park was supported by a fund from the Science and Technology Planning Project of Jiaxing (no. 2008AZ1024). Dr. Jun-Mo Yang was supported by the grants of the Korea Health 21 R&D Project (Ministry of Health, Welfare and Family Affairs, Republic of Korea, 01-PJ3-PG6-01GN12-0001 and A030003).

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Authors and Affiliations

  1. Department of Biological Science and Biotechnology, Tsinghua University, Beijing, 100084, People’s Republic of China

    Hang Mu, He-Chang Zou & Hai-Meng Zhou

  2. Department of Environmental Health, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China

    Zhi-Rong Lü, Fei Zou & Yong-Doo Park

  3. Korean BioInformation Center (KOBIC), KRIBB, Daejeon, 305-806, South Korea

    Daeui Park, Byoung-Chul Kim & Jong Bhak

  4. Department of Dermatology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, 135-710, South Korea

    Jun-Mo Yang

  5. Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, Beijing, 100875, People’s Republic of China

    Sen Li

  6. 9F, Innovation Tower,705 Ya Tai Road, Jiaxing, 314006, China

    He-Chang Zou

  7. Haidian District, Department of Biological Science and Biotechnology, Tsinghua University, Beijing, 100084, China

    Hai-Meng Zhou

Authors
  1. Hang Mu
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  2. Zhi-Rong Lü
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  3. Daeui Park
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  4. Byoung-Chul Kim
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  5. Jong Bhak
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  6. Fei Zou
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  8. Sen Li
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  9. Yong-Doo Park
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  10. He-Chang Zou
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Corresponding authors

Correspondence to He-Chang Zou or Hai-Meng Zhou.

Additional information

H. Mu and Z.-R. Lü are equally contributed to this study.

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Mu, H., Lü, ZR., Park, D. et al. Kinetics of Zn2+-induced Brain Type Creatine Kinase Unfolding and Aggregation. Appl Biochem Biotechnol 160, 1309–1320 (2010). https://doi.org/10.1007/s12010-009-8574-3

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  • DOI: https://doi.org/10.1007/s12010-009-8574-3

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