Skip to main content
SpringerLink
Log in

The Occluded Nucleotide Conformation of P-Glycoprotein

  • Published:
Journal of Bioenergetics and Biomembranes Aims and scope Submit manuscript

 

We review recent work on E552A/E1197A P-glycoprotein. This ATPase-defective mutant occludes MgATP tightly with maximal 1/1 stoichiometry in drug-sensitive fashion. The occluded nucleotide conformation appears to represent a transient, asymmetric, catalytic intermediate. We present a model for catalysis incorporating nucleotide binding domain (NBD) dimerization and the occluded nucleotide conformation, and we speculate as to how catalysis seen in P-glycoprotein might be harmonized with symmetrical dimer structures of isolated NBDs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

Pgp:

P-glycoprotein

NBD:

nucleotide binding domain

TMD:

transmembrane domain

Vi:

orthovanadate

BeFx:

beryllium fluoride

References

  • Chen, J., Lu, G., Lin, J., Davidson, A. L., and Quiocho, F. A. (2003). Mol. Cell 12, 651–661.

    Article  CAS  Google Scholar 

  • Chen, J., Sharma, S., Quiocho, F. A., and Davidson, A. L. (2001). Proc. Natl. Acad. Sci. U.S.A. 98, 1525–1530.

    Article  CAS  Google Scholar 

  • Hopfner, K. P., Karcher, A., Shin, D. S., Craig, L., Arthur, L. M., Carney, J. P., and Tainer, J. A. (2000). Cell 101, 789–800.

    Article  CAS  Google Scholar 

  • Horn, C., Bremer, E., and Schmitt, L. (2003). J. Mol. Biol. 334, 403–419.

    Article  CAS  Google Scholar 

  • Janas, E., Hofacker, M., Chen, M., Gompf, S., van der Does, C., and Tampé, R. (2003). J. Biol. Chem. 278, 26862–26869.

    Article  CAS  Google Scholar 

  • Lee, J. Y., Urbatsch, I. L., Senior, A. E., and Wilkens, S. (2002). J. Biol. Chem. 277, 40125–40131.

    Article  CAS  Google Scholar 

  • Locher, K. P., Lee, A. T., and Rees, D. C. (2002). Science 296, 1091–1098.

    Article  CAS  Google Scholar 

  • Loo, T. W., Bartlett, M. C., and Clarke, D. M. (2002). J. Biol. Chem. 277, 41303–41306.

    Article  CAS  Google Scholar 

  • Moody, J. E., Millen, L., Binns, D., Hunt, J. F., and Thomas, P. J. (2002). J. Biol. Chem. 277, 21111–21114.

    Article  CAS  Google Scholar 

  • Oloo, E. O., and Tieleman, D. P. (2004). J. Biol. Chem. 279, 45013–45019.

    Article  CAS  Google Scholar 

  • Orelle, C., Dalmas, O., Gros, P., Di Pietro, A., and Jault, J. M. (2003). J. Biol. Chem. 278, 47002–47008.

    Article  CAS  Google Scholar 

  • Qu, Q., Russell, P. L., and Sharom, F. J. (2003). Biochemistry 42, 1170–1177.

    Article  CAS  Google Scholar 

  • Reyes, C., and Chang, G. (2005). Science 308, 1028–1031.

    Article  CAS  Google Scholar 

  • Rosenberg, M. F., Callaghan, R., Modok, S., Higgins, C. F., and Ford, R. C. (2005). J. Biol. Chem. 280, 2857–2862.

    Article  CAS  Google Scholar 

  • Sankaran, B., Bhagat, S., and Senior, A. E. (1997). Biochemistry 36, 6847–6853.

    Article  CAS  Google Scholar 

  • Senior, A. E., Al-Shawi, M. K., and Urbatsch, I. L. (1995). FEBS Lett. 377, 285–289.

    Article  CAS  Google Scholar 

  • Sharma, S., and Davidson, A. L. (2000). J. Bacteriol. 182, 6570– 6576.

    Article  CAS  Google Scholar 

  • Smith, P. C., Karpowich, N., Millen, L., Moody, J. E., Rosen, J., Thomas, P. J., and Hunt, J. F. (2002). Mol. Cell 10, 139– 149.

    Article  CAS  Google Scholar 

  • Tombline, G., Bartholomew, L., Gimi, K., Tyndall, G. A., and Senior, A. E. (2004b). J. Biol. Chem. 279, 5363–5373.

    Article  CAS  Google Scholar 

  • Tombline, G., Bartholomew, L., Urbatsch, I. L., and Senior, A. E. (2004a). J. Biol. Chem. 279, 31212–31220.

    Article  CAS  Google Scholar 

  • Tombline, G., Muharemagic, A., White, L. B., and Senior, A. E. (2005). Biochemistry 44, 12879–12886.

    Article  CAS  Google Scholar 

  • Urbatsch, I. L., Beaudet, L., Carrier, I., and Gros, P. (1998). Biochemistry 37, 4592–4602.

    Article  CAS  Google Scholar 

  • Urbatsch, I. L., Gimi, K., Wilke-Mounts, S., and Senior, A. E. (2000a). J. Biol. Chem. 275, 25031–25038.

    Article  CAS  Google Scholar 

  • Urbatsch, I. L., Gimi, K., Wilke-Mounts, S., and Senior, A. E. (2000b). Biochemistry 39, 11921–11927.

    Article  CAS  Google Scholar 

  • Urbatsch, I. L., Gimi, K., Wilke-Mounts, S., Lerner-Marmarosh, N., Rousseau, M.-E., Gros, P., and Senior, A. E. (2001). J. Biol. Chem. 276, 26980–26987.

    Article  CAS  Google Scholar 

  • Urbatsch, I. L., Sankaran, B., Bhagat, S., and Senior, A. E. (1995). J. Biol. Chem. 270, 26956–26961.

    Article  CAS  Google Scholar 

  • Verdon, G., Albers, S. V., van Oosterwijk, N., Dijkstra, B. W., Driessen, A. J. M., and Thunnisen, A. M. W. H. (2003). J. Mol. Biol. 334, 255–267.

    Article  CAS  Google Scholar 

  • Zaitseva, J., Jenewein, S., Jumpertz, T., Holland, I. B., and Schmitt, L. (2005a). EMBO J. 24, 1901–1910.

    Article  CAS  Google Scholar 

  • Zaitseva, J., Jenewein, S., Wiedenmann, A., Benabdelhak, H., Holland, I. B., and Schmitt, L. (2005b). Biochemistry 44, 9680– 9690.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry and Biophysics, University of Rochester Medical Center, Box 712, Rochester, New York, 14642

    Gregory Tombline & Alan E. Senior

Authors
  1. Gregory Tombline
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alan E. Senior
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alan E. Senior.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tombline, G., Senior, A.E. The Occluded Nucleotide Conformation of P-Glycoprotein. J Bioenerg Biomembr 37, 497–500 (2005). https://doi.org/10.1007/s10863-005-9498-4

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10863-005-9498-4

Key Words

Search

Navigation