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Crystal structure of human cathepsin K complexed with a potent inhibitor

The high resolution structure of the new therapeutic target, cathepsin K, complexed with the potent mechanism-based inhibitor, APC3328, reveals the substrate-binding sites of this cysteine proteinase and validates the binding mode for this inhibitor class.

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References

  1. Delaisse, J.-M. et al. Bone 8, 305–313 (1987).

    Article  CAS  PubMed  Google Scholar 

  2. Everts, V., Beertsen, W. & Schröder R Calcif. Tissue Int. 43, 172–178 (1988).

    Article  CAS  PubMed  Google Scholar 

  3. Delaisse, J.-M. & Vaes, G. in Biology and Physiology of the Osteoclast (eds. Rifkin, B.R. & Gay, C.V.) 289–314 (CRC Press, Boca Raton, FL, 1992).

    Google Scholar 

  4. Tezuka, K. et al. J. Biol. Chem. 269, 1106–1109 (1994).

    CAS  PubMed  Google Scholar 

  5. Drake, F.H. et al. J. Biol. Chem. 271, 12511–12516 (1996).

    Article  CAS  PubMed  Google Scholar 

  6. Brömme, D. & Okamoto, K. Biol. Chem. Hoppe-Seyler 376, 379–384 (1995).

    Article  PubMed  Google Scholar 

  7. Brömme, D., Okamoto, K., Wang, B.B. & Biroc, S. J. Biol. Chem. 271, 2126–2132 (1996).

    Article  PubMed  Google Scholar 

  8. Bossard, M.J. et al. J. Biol. Chem. 271, 12517–12524 (1996).

    Article  CAS  PubMed  Google Scholar 

  9. Polymeropoulos, M.H. et al. Nature Genetics 10, 238–239 (1995).

    Article  CAS  PubMed  Google Scholar 

  10. Gelb, B.D., Edelson, J.G. & Desnick, R.J. Nature Genetics 10, 235–237 (1995).

    Article  CAS  PubMed  Google Scholar 

  11. Gelb, B.D., Shi, G.-P., Chapman, H.A. & Desnick, R.J. Science 273, 1236–1238 (1996).

    Article  CAS  PubMed  Google Scholar 

  12. Berti, P.J. & Storer, A.C. J. Mol. Biol. 246, 273–283 (1995).

    Article  CAS  PubMed  Google Scholar 

  13. Polgar, L. FEBS Lett. 47, 15–18 (1974).

    Article  CAS  PubMed  Google Scholar 

  14. Rullmann, J.A.C., Bellido, M.N. & van Duijnen, P.T. J. Mol. Biol. 206 (1989).

  15. Kamphuis, I.G., Kalk, K.H., Swarte, M.B.A. & Drenth, J. J. Mol. Biol. 179, 233–256 (1984).

    Article  CAS  PubMed  Google Scholar 

  16. McGrath, M.E. et al. J. Mol. Biol. 247, 251–259 (1995).

    Article  CAS  PubMed  Google Scholar 

  17. Musil, D. et al. EMBO J. 10, 2321–2330 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Turk, D. et al. Biochemistry 34, 4791–4797 (1995).

    Article  CAS  PubMed  Google Scholar 

  19. Jia, Z. et al. J. Biol. Chem. 270, 5527–5533 (1995).

    Article  CAS  PubMed  Google Scholar 

  20. Palmer, J.T., Rasnick, D. & Klaus, J.L. J. Med. Chem. 38, 3193–3196 (1995).

    Article  CAS  PubMed  Google Scholar 

  21. Yamamoto, D. et al. J. Biol. Chem. 266, 14771–14777 (1991).

    CAS  PubMed  Google Scholar 

  22. Drenth, J., Kalk, K.H. & Swen, H.M. Biochemistry 15, 3731–3738 (1976).

    Article  CAS  PubMed  Google Scholar 

  23. Cygler, M. et al. Structure 4, 405–416 (1996).

    Article  CAS  PubMed  Google Scholar 

  24. Coulombe, R. et al. EMBO J. 15, 5492–5503 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. James, M.N.G. in Keystone Symposium on the Structural and Molecular Biology of Proteinase Function and Inhibition (Sante Fe, New Mexico, 1994).

    Google Scholar 

  26. Kirschke, H., Wiederanders, B., Brömme, D. & Rinne, A. Biochem. J. 264, 467–473 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Brömme, D. et al. J. Biol. Chem. 268, 4832–4838 (1993).

    PubMed  Google Scholar 

  28. Pickersgill, R.W., Goodenough, P.W., Sumner, I.G. & Collins, M.E. Biochem. J. 254, 235–238 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Taylor, M.A.J. et al. Protein Engng. 7, 1267–1276 (1994).

    Article  CAS  Google Scholar 

  30. Collaborative Computational Project, Num. 4 Acta Crystallogr. D50, 760–763 (1994).

  31. McRee, D.E. Practical Protein Crystallography (Academic Press, New York, 1993).

    Google Scholar 

  32. Brünger, A.T. X-PLOR Version 3.1, Manual (Yale University, 1992).

    Google Scholar 

  33. Luthy, R., Bowie, J.U. & Eisenberg, D. Nature 356, 83–85 (1992).

    Article  CAS  PubMed  Google Scholar 

  34. Bernstein, F.C. et al. J. Mol. Biol. 112, 535–542 (1977).

    Article  CAS  PubMed  Google Scholar 

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McGrath, M., Klaus, J., Barnes, M. et al. Crystal structure of human cathepsin K complexed with a potent inhibitor. Nat Struct Mol Biol 4, 105–109 (1997). https://doi.org/10.1038/nsb0297-105

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