Abstract
Cyclin-dependent kinase 2 (CDK2) is a member of a highly conserved family of protein klnases that regulate the eukaryotic cell cycle. The crystal structures of the human CDK2 apoenzyme and its Mg2+ATP complex have been determined to 2.4Å resolution. The structure is bi-lobate, like that of the cyclic AMP-dependent protein kinase, but contains a unique helix—loop segment that interferes with ATP and protein substrate binding and probably plays a key part in the regulation of all cyclin-dependent kinases.
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References
Norbury, C. & Nurse, P. A. Rev. Biochem. 61, 441–470 (1992).
Forsburg, S. L. & Nurse, P. A. Rev. Cell Biol. 7, 227–256 (1991).
Fang, F. & Newport, J. W. Cell 66, 731–742 (1991).
Pagano, M. et al. J. Cell Biol. 121, 101–111 (1993).
Hanks, S. K. & Quinn, A. M. Meth. Enzym. 200, 38–62 (1991).
Hunt, T. Curr. Opin. Cell Biol. 1, 286–274 (1989).
Desai, D., Gu, Y. & Morgan, D. O. Molec. Biol. Cell 3, 571–582 (1992).
Connell-Crowley, L., Solomon, M. J., Wei, N. & Harper, J. W. Molec. Biol. Cell 4, 79–92 (1993).
Solomon, M. J., Lee, T. & Kirschner, M. W. Molec. Biol. Cell 3, 13–27 (1992).
Gu, Y., Rosenblatt, J. & Morgan, D. O. EMBO J. 11, 3995–4005 (1992).
Gould, K. L., Moreno, S., Owen, D. J., Sazer, S. & Nurse, P. EMBO J. 10, 3297–3309 (1991).
Krek, W. & Nigg, E. A. EMBO J. 10, 3331–3341 (1991).
Norbury, C., Blow, J. & Nurse, P. EMBO J. 10, 3321–3329 (1991).
Parker, L. L., Atherton-Fessler, S. & Piwnica-Worms, H. Proc. natn. Acad. Sci. U.S.A. 89, 2917–2921 (1992).
McGowan, C. H. & Russell, P. EMBO J. 12, 75–85 (1993).
Knighton, D. R. et al. Science 253, 414–420 (1991).
Knighton, D. R. et al. Science 253, 407–414 (1991).
Zheng, J. et al. Biochemistry 32, 2154–2161 (1993).
Zheng, J. et al. Acta crystallogr. D49, 363–365 (1993).
Rosenblatt, J., De Bondt, H., Jancarik, J., Morgan, D. O. & Kim, S.-H. J. molec. Biol. 230, 1317–1319 (1993).
Yoon, M.-Y. & Cook, P. F. Biochemistry 26, 4118–4125 (1987).
Ho, M.-F., Bramson, H. N., Hansen, D. E., Knowles, J. R. & Kaiser, E. T. J. Am. Chem. Soc. 110, 2680–2681 (1988).
Atherton-Fessler, S., Parker, L. L., Geahlen, R. L. & Piwnica-Worms, H. Molec. cell Biol. 13, 1675–1685 (1993).
Ducommun, B. et al. EMBO J. 10, 3311–3319 (1991).
Richardson, H. E., Stueland, C. S., Thomas, J., Russell, P. & Reed, S. I. Genes Dev. 4, 1332–1344 (1990).
Ducommun, B., Brambilla, P. & Draetta, G. Molec. cell. Biol. 11, 6177–6184 (1991).
Ayscough, K. Hayles, J., MacNeill, S. A. & Nurse, P. Molec. gen. Genet. 232, 344–350 (1992).
Carr, A. M., MacNeill, S. A., Hayles, J. & Nurse, P. Molec. gen. Genet. 218, 41–49 (1989).
Lorincz, A. T. & Reed, S. I. Molec. cell. Biol. 6, 4099–4103 (1986).
MacNeill, S. A., Creanor, J. & Nurse, P. Molec. gen. Genet. 229, 109–118 (1991).
Booher, R. N., Alfa, C. E., Hyams, J. S. & Beach, D. H. Cell 58, 485–497 (1989).
Moreno, S., Hayles, J. & Nurse, P. Cell 58, 361–372 (1989).
Payne, D. M. et al. EMBO J. 10, 885–892 (1991).
Kmiecik, T., Johnson, P. J. & Shalloway, D. Molec. cell. Biol. 8, 4541–4546 (1988).
Ellis, L. et al. Cell 45, 721–732 (1986).
Matthews, B. W. J. molec. Biol 33, 491–497 (1968).
Furey, W. PHASES Manual (Univ. Pittsburgh, PA, 1992).
Wang, B. C. Meth. Enzym. 115, 90–112 (1985).
Jones, T. A., Zou, J.-Y., Cowan, S. W. & Kjeldgaard, N. Acta crystallogr. A47, 110–119 (1991).
Brunger, A. T. XPLOR, a System for Crystallography and NMR, Version 3.0 Manual (Yale Univ., New Haven, CT, 1991).
Petsko, G. A. Meth. Enzym. 114, 147–156 (1985).
Kraulis, P. J. J. appl. crystallogr. 24, 946–950 (1991).
Tsai, L.-H., Harlow, E. & Meyerson, M. Nature 353, 174–177 (1991).
Lee, M. G. & Nurse, P. Nature 327, 31–35 (1987).
Hindley, J. & Phear, G. A. Gene 31, 129–134 (1984).
Lorincz, A. T. & Reed, S. I. Nature 307, 183–185 (1984).
Kabsch, W. & Sander, C. Biopolymers 22, 2577–2637 (1983).
Rose, G. D., Geselowitz, A. R., Lesser, G. J., Lee, R. H. & Zehfus, M. H. Science 229, 834–838 (1985).
Kobayashi, H. et al. Molec. Biol. Cell 3, 1279–1294 (1992).
Lees, E. M. & Harlow, E. Molec. cell. Biol. 13, 1194–1201 (1993).
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De Bondt, H., Rosenblatt, J., Jancarik, J. et al. Crystal structure of cyclin-dependent kinase 2. Nature 363, 595–602 (1993). https://doi.org/10.1038/363595a0
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DOI: https://doi.org/10.1038/363595a0
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