Effects of zinc on creatine kinase: activity changes, conformational changes, and aggregation.
The effects of zinc on creatine kinase (CK) are very distinctive compared with other bivalent metal ions. Zinc up to 0.1 mM induced increases in CK activity, accompanied by significant hydrophobic surface exposure and increase in alpha-helix content of CK. Zinc over 0.1 mM denatured and inactived CK. In the presence of 0.1 mM zinc, the CK activity was very close to that of the native CK, but its conformation changed greatly. The kinetic courses of CK inactivation and conformational change in the presence of 1 mM zinc were measured to determine apparent rate constants of inactivation and conformational change. Zinc over 0.05 mM induced CK aggregation at 37 degrees C, and the aggregation was dependent on zinc concentration, CK concentration, and temperature. The inactivation and aggregation can be reversed by EDTA. An explanation for CK aggregation induced by zinc is proposed, as well as a mechanism for CK abnormality in Alzheimer's disease.
Department of Biological Science and Biotechnology, School of Life Science and Engineering, Tsinghua University, Beijing, China.
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Tong
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Zeng
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Zhou
D000544:Alzheimer Disease / Q000209:etiology; D000818:Animals; D002942:Circular Dichroism; D003402:Creatine Kinase / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D011487:Protein Conformation / Q000187:drug effects; D011489:Protein Denaturation / Q000187:drug effects; D017433:Protein Structure, Secondary / Q000187:drug effects; D011817:Rabbits; D013050:Spectrometry, Fluorescence; D013696:Temperature; D015032:Zinc / Q000737:chemistry / Q000494:pharmacology*
D003402:Creatine Kinase; D015032:Zinc