Abstract
The crystal structure of the human p27Kip1 kinase inhibitory domain bound to the phosphorylated cyclin A–cyclin-dependent kinase 2 (Cdk2) complex has been determined at 2.3 Å. p27Kip1 binds the complex as an extended structure interacting with both cyclin A and Cdk2. On cyclin A, it binds in a groove formed by conserved cyclin box residues. On Cdk2, it binds and rearranges the amino-terminal lobe and also inserts into the catalytic cleft, mimicking ATP.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Pines, J. Cancer Biol. 6, 63–72 (1995).
Peter, M. & Herskowitz, I. Cell 79, 181–184 (1994).
Sherr, C. J. & Roberts, J. M. Genes Dev. 9, 1149–1163 (1995).
Polyak, K. et al. Cell 78, 59–66 (1994).
Reynisdóttir, I., Polyak, K., lavarone, A. & Massagué, J. Genes Dev. 9, 1831–1845 (1995).
Parker, S. B. et al. Science 267, 1024–1027 (1995).
Liu, M., Lee, M. H., Cohen, M., Bommakanti, M. & Freedman, L. P. Genes Dev. 10, 142–153 (1996).
Lee, M. H. et al. Proc. natn. Acad. Sci. U.S.A. 93, 3259–3263 (1996).
EI-Deiry, W. S. et al. Cell 75, 817–825 (1993).
Soos, T. J. et al. Cell Growth Differ. 7, 135–146 (1996).
Poon, R. Y. C., Toyoshima, H. & Hunter, T. Molec. biol. Cell 6, 1197–1213 (1995).
Toyoshima, H. & Hunter, T. Cell 78, 67–74 (1994).
Xiong, T. et al. Nature 366, 701–704 (1993).
Gu, Y., Turck, C. W. & Morgan, D. O. Nature 366, 707–710 (1993).
Harper, J. W., Adami, G. R., Wei, N., Keyomarsi, K. & Elledge, S. J. Cell 75, 805–816 (1993).
Lee, M. H., Reynisdóttir, I. & Massagué, J. Genes Dev. 9, 639–649 (1995).
Matsuoka, S. et al. Genes Dev. 9, 650–662 (1995).
Chen, J., Jackson, P. K., Kirschner, M. W. & Dutta, A. Nature 374, 386–388 (1995).
Lin, J., Reichner, C., Wu, X. & Levine, A. J. Molec. cell. Biol. 16, 1786–1793 (1996).
Harper, J. W. et al. Molec. Biol. Cell 6, 387–400 (1995).
Luo, Y., Hurwitz, J. & Massagué, J. Nature 375, 159–161 (1995).
Jeffrey, P. D. et al. Nature 375, 159–161 (1995).
Russo, A. R., Jeffrey, P. D. & Pavletich, N. P. Nature struct. Biol. (in the press).
Chothia, C. J. molec. Biol. 105, 1–14 (1976).
Zhu, L., Harlow, E. & Dynlachtt, D. Genes Dev. 9, 1740–1752 (1995).
Chen, I. et al. Oncogene 12, 595–607 (1996).
Fisher, R. P. & Morgan, D. O. Cell 78, 713–724 (1994).
Kato, J., Matsuoka, M., Polyak, K., Massagué, J. & Sherr, C. J. Cell 79, 487–496 (1994).
Aprelikova, O., Xiong, Y. & Liu, E. T. J. biol. Chem. 270, 18195–18197 (1995).
Nikolic, M., Dudek, H., Kwon, Y. T., Ramos, Y. K. & Tsai, L. H. Genes Dev. 10, 816–825 (1996).
Zhang, H., Hannon, G. J. & Beach, D. Genes Dev. 8, 1570–1758 (1994).
Navaza, J. Acta Crystallogr. A50, 157–163 (1994).
Collaborative Computational Project No. 4. Acta Crystallogr. D50, 760–763 (1994).
Brunger, A. T. X-PLOR, a System for Crystallography and NMR Version 3.0 Manual (Yale Univ. Press, New Haven, CT, 1991).
Tonrud, D. E., Ten Eyck, L. F. & Matthews, B. W. Acta Crystallogr. A43, 489 (1987).
Kraulis, P. J. J. appl. Crystallogr. 24, 946–950 (1991).
Merrit, E. A. & Murphy, M. E. Acta Crystallogr. D50, 869–873 (1994).
Nicholls, A., Sharp, K. A. & Honig, B. Proteins Struct. Funct. Genet. 11, 281–296 (1991).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Russo, A., Jeffrey, P., Patten, A. et al. Crystal structure of the p27Kip1 cyclin-dependent-kinase inibitor bound to the cyclin A–Cdk2 complex . Nature 382, 325–331 (1996). https://doi.org/10.1038/382325a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/382325a0
