Abstract
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 a-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°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.
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REFERENCES
Atwood, C. S., Moir, R. D., Huang, X., Scarpa, R. C., Bacarra, N. M., Romano, D. M., Hartshorn, M. A., Tanzi, R. E., and Bush, A. I. (1998). J. Biol. Chem. 273, 12817–12826.
Baksh, S., Spamer, C., Oikawa, K., McCubbin, W. D., Heilmann, C., Kay, C. M., and Michalak, M. (1995). Biochem. Biophys. Res. Commun. 209, 310–315.
Brazil, B. T., Ybarra, J., and Horowitz, P. M. (1998). J. Biol. Chem. 273, 3257–3263.
Brown, A. M., Tummolo, D. M., Rhodes, K. J., Hofmann, J. R., Jacobsen, J. S., and Sonnenberg-Reines, J. (1997). J. Neurochem. 69, 1204–1212.
Cao, Z. F., Luo, W., and Zhou, H. M. (1999). Int. J. Biochem Cell. Biol. 31, 1307–1313.
Cavatorta, P., Giovanelli, S., Bobba A., Riccio, P., Szabo, A. G., and Quagliariello, E. (1994). Biophys. J. 66, 1174–1179.
Chaoui, A., Mazhoudi, S., Ghorbal, M. H., and Elferjani, E. (1997). Plant Sci. 127, 139–147.
David, S., Shoemaker, M., and Haley, B. E. (1998). Brain. Res. Mol. Brain. Res. 54, 276–287.
Fritz-Wolf, K., Schnyder, T., Wallimann, T., and Kabsch. W. (1996). Nature 381, 341–345.
Gerhardt, W. (1983). In Methods in Enzymatic Analysis, 3rd ed. (Bergmeyer, H. U., ed.), Verlag Chemie, Weinheim, Vol. 3, pp. 508–510.
Hershenson, S., Hermers, P., Desmueles, P., and Stroud, R. (1986). J. Biol. Chem. 261, 3732–3736.
Jaxobus, W. E. (1985). Annu. Rev. Physiol. 47, 707–725.
Khanna, N. C., Tokuda, M., and Waisman, D. M. (1986). J. Biol. Chem. 261, 8883–8887.
Liu, S. T., Howllet, G., and Barrow, C. J. (1999). Biochemistry 38, 9373–9378.
Morrison, J. F. and O'sullivan, W. J. (1965). Biochem. J. 97, 37–57.
Mühlebach, S. M., Gross, M., Wirz, T., Walliamann, T., Perriard, J.-C., and Wyss, M. (1994). Mol. Cell Biochem. 133/134, 245–262.
Nakagawa, T. and Nagayama, F. (1991). Comp. Biochem. Physiol. B Comp. Biochem. 98B, 349–354.
Rao, J. K., Bujacz, G., and Wlodawer, A. (1998). FEBS Lett. 439, 133–137.
Schmalz, G., Arenholtbindslev, D., Hiller, K. A., and Schweikl H. (1997). Eur. J. Oral Sci. 105, 86–91.
Tanford, C. (1968). Adv. Protein Chem. 23, 121–282.
Vallee, B. L. and Auld, D. S. (1990). Biochemistry 29, 5647–5659.
Vallee, B. L. and Auld, D. S. (1993). Biochemistry 32, 6493–6500.
Vallee, B. L. and Auld, D. S. (1995). EXS 73, 259–277.
Wang, Z. F., Huang, M. Q., Zou, X. M., and Zhou, H. M. (1995a). Biochim. Biophys. Acta 1251, 109–114.
Wang, Z. F., Yang, Y., and Zhou, H. M. (1995b). Biochimie 77, 953–956.
Watts, D. C. (1973). In The Enzymes (Boyer, P. D., ed.) Academic Press, New York, Vol. 8, pp. 383–445.
Wu, H. B. and Tsou, C. L. (1993). Biochem. J. 296, 435–441.
Yang, Y., Park, Y. D., Yu, T. W., and Zhou, H. M. (1999). Biochem. Biophys. Res. Commun. 259, 450–454.
Yao, Q. Z., Zhou, H. M., Hou, L. X., and Tsou, C. L. (1982a) Sci. Sin. (Engl. Ed.) 25, 1186–1193.
Yao, Q. Z., Hou, L. X., Zhou, H. M., and Tsou, C. L. (1982b). Sci. Sin. (Engl. Ed.) 25, 1296–1302.
Yao, Q. Z., Tian, M., and Tsou, C. L. (1984). Biochemistry 23, 2740–2744.
Zettlmeissl, G., Rudolph, R., and Jaenicke, R. (1979). Biochemistry 18, 5567–5571.
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Tong, X., Zeng, X. & Zhou, HM. Effects of Zinc on Creatine Kinase: Activity Changes, Conformational Changes, and Aggregation. J Protein Chem 19, 553–562 (2000). https://doi.org/10.1023/A:1007142117037
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DOI: https://doi.org/10.1023/A:1007142117037