Abstract
The crystal structure of mammalian protein phosphatase-1, complexed with the toxin microcys-tin and determined at 2.1 Å resolution, reveals that it is a metalloenzyme unrelated in architecture to the tyrosine phosphatases. Two metal ions are positioned by a central β-α-β-α-β scaffold at the active site, from which emanate three surface grooves that are potential binding sites for substrates and inhibitors. The carboxy terminus is positioned at the end of one of the grooves such that regulatory sequences following the domain might modulate function. The fold of the catalytic domain is expected to be closely preserved in protein phosphatases 2A and 2B (calcineurin).
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References
Fischer, E. H. & Brautigan, D. L. Trends biochem. Sci. 3–4 (1982).
Cohen, P. A. Rev. Biochem. 58, 453–508 (1989).
Shenolikar, S. A. Rev. Cell Biol. 10, 55–86 (1994).
Ingebritsen, T. S. & Cohen, P. Eur. J. Biochem. 132, 255–261 (1983).
Zhuo, S., Clemens, J. C., Stone, R. L. & Dixon, J. E. J. biol. Chem. 269, 26234–26238 (1994).
Hubbard, M. J. & Cohen, P. Trends biochem. Sci. 18, 172–177 (1993).
Hemmings, H. C. J., Nairn, A. C., Bibb, J. A. & Greengard, P. in Molecular and Cellular Mechanisms of Neostriatal Function (eds Ariano, M. A. & Surmeier, D. J.) 279–293 (Landes, Austin, TX, 1995).
Dohadwala, M. et al. Proc. natn. Acad. Sci. U.S.A. 91, 6408–6412 (1994).
Yamano, H., Ishii, K. & Yanagida, M. EMBO J. 13, 5310–5318 (1994).
Klee, C. B., Draetta, G. F. & Hubbard, M. J. in Advances in Enzymology and Related Areas of Molecular Biology (ed. Meister, A.) 149–209 (Wiley, New York, 1988).
Kincaid, R. L., Nightingale, M. S. & Martin, B. M. Proc. natn. Acad. Sci. U.S.A. 85, 8983–8987 (1988).
Holmes, C. F. B. & Boland, M. P. Curr. Opin. struct. Biol. 3, 934–943 (1993).
Suganuma, M. et al. Proc. natn. Acad. Sci. U.S.A. 85, 1768–1771 (1988).
Nishiwaki-Matsushima, R. et al. J. Cancer. Res. clin. Oncol. 118, 420–424 (1992).
Schreiber, S. L. Cell 70, 365–368 (1992).
Hendrickson, W. A. Science 254, 51–58 (1991).
Barton, G. J., Cohen, P. T. W. & Barford, D. Eur. J. Biochem. 220, 225–237 (1994).
Jenny, T. F., Gerloff, D. L. & Benner, S. A. Proteins 21, 1–10 (1995).
Beese, L. S. & Steitz, T. A. EMBO J. 10, 25–33 (1991).
Kim, E. E. & Wyckoff, H. W. J. molec. Biol. 218, 449–464 (1991).
Sträter, N., Klabunde, T., Tucker, P., Witzel, H. & Krebs, B. Science 268, 1489–1492 (1995).
King, M. M. & Huang, C. Y. J. biol. Chem. 259, 8847–8856 (1984).
Vincent, J. B., Crowder, M. W. & Averill, B. A. Trends biochem. Sci. 17, 105–110 (1992).
Alessi, D. R., Street, A. J., Cohen, P. & Cohen, P. T. Eur. J. Biochem. 213, 1055–1066 (1993).
Koonin, E. V. Protein Sci. 3, 356–358 (1994).
Kim, Y., Huang, J., Cohen, P. & Matthews, H. R. J. biol. Chem. 268, 18513–18518 (1993).
Cayla, X., Ballmer-Hofer, K., Merlevede, W. & Goris, J. Eur. J. Biochem. 15, 281–286 (1993).
Vincent, J. B., Crowder, M. W. & Averill, B. A. J. biol. Chem. 266, 17737–17740 (1991).
Moorhead, G., MacKintosh, R. W., Morrice, N., Gallagher, T. & MacKintosh, C. FEBS Lett. 356, 46–50 (1994).
Zhang, Z., Zhao, S., Deans-Zirattu, S., Bai, G. & Lee, E. Y. C. Molec. cell. Biochem. 128, 113–119 (1993).
Bagu, J. R. et al. Nature struct. Biol. 2, 114–116 (1995).
Cardenas, M. E., Muir, R. S., Breuder, T. & Heitman, J. EMBO J. 14, 2772–2783 (1995).
MacKintosh, C., Beattie, K. A., Klumpp, S., Cohen, P. & Codd, G. A. FEBS Lett. 264, 187–192 (1990).
Zhang, Z. et al. J. biol. Chem. 269, 16997–17000 (1994).
Stone, R. L. & Dixon, J. E. J. biol. Chem. 269, 31323–31326 (1994).
Cohen, P. T. W. FEBS Lett. 232, 17–23 (1988).
Stone, S. et al. Nucleic Acids Res. 16, 11365 (1988).
Guerini, D. & Klee, C. B. Proc. natn. Acad. Sci. U.S.A. 86, 9183–9187 (1989).
Cohen, P. T. W. & Cohen, P. Biochem. J. 260, 931–934 (1989).
Watanabe, Y., Perrino, B. A., Chang, B. H. & Soderling, T. R. J. biol. Chem. 270, 456–460 (1995).
Hashimoto, Y., Perrino, B. A. & Soderling, T. R. J. biol. Chem. 265, 1924–1927 (1990).
Barford, D. & Keller, J. C. J. molec. Biol. 235, 763–766 (1994).
Brünger, A. T. Acta crystallogr. D49, 24–36 (1993).
Zhang, K. Y. J. & Main, P. Acta crystallogr. A46, 377–381 (1990).
Kleywegt, G. J. & Jones, T. A. in Proc. CCP4 Study Weekend 59–66 (SERC Daresbury Laboratory, Warrington, UK, 1994).
Jones, T. A., Zou, J. Y., Cowan, S. W. & Kjeldgaard, M. Acta crystallogr. A47, 110–119 (1991).
Kraulis, P. J. appl. Crystallogr. 24, 946–950 (1991).
Bacon, D. J. & Anderson, W. F. J. molec.-Graph. 6, 219–220 (1988).
Nicholls, A., Sharp, K. A. & Honig, B. Prot. Struct. Funct. Genet. 11, 281–296 (1991).
Brünger, A. T., Krukowski, A. & Erickson, J. W. Acta crystallogr. A46, 585–593 (1990).
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Goldberg, J., Huang, Hb., Kwon, Yg. et al. Three-dimensional structure of the catalytic subunit of protein serine/threonine phosphatase-1. Nature 376, 745–753 (1995). https://doi.org/10.1038/376745a0
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DOI: https://doi.org/10.1038/376745a0
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