Allosteric modulation bypasses the requirement for ATP hydrolysis in regenerating low affinity transition state conformation of human P-glycoprotein

The Journal of Biological Chemistry
Nazli MakiS Dey

Abstract

ATP-dependent drug transport by human P-glycoprotein (Pgp, ABCB1) involves a coordinated communication between its drug-binding site (substrate site) and the nucleotide binding/hydrolysis domain (ATP sites). It has been demonstrated that the two ATP sites of Pgp play distinct roles within a single catalytic turnover; whereas ATP binding or/and hydrolysis by one drives substrate translocation and dissociation, the hydrolytic activity of the other resets the transporter for the subsequent cycle (Sauna, Z. E., and Ambudkar, S. V. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 2515-2520; Sauna, Z. E., and Ambudkar, S. V. (2001) J. Biol. Chem. 276, 11653-11661). Trapping of ADP (or 8-azido-ADP) and vanadate (ADP.Vi or 8-azido-ADP.Vi) at the catalytic site, following nucleotide hydrolysis, markedly reduces the affinity of Pgp for its transport substrate [125I]iodoarylazidoprazosin ([125I]IAAP), resulting in dissociation of the latter. Regeneration of the [125I]IAAP site requires an additional round of nucleotide hydrolysis. In this study, we demonstrate that certain thioxanthene-based allosteric modulators, such as cis-(Z)-flupentixol and its closely related analogs, induce regeneration of [125I]IAAP binding to vanadate-trapped (or fluor...Continue Reading

References

Jan 1, 1992·Annual Review of Cell Biology·C F Higgins
Sep 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·S V AmbudkarI Pastan
Nov 10, 1995·The Journal of Biological Chemistry·I L UrbatschA E Senior
Aug 18, 1995·The Journal of Biological Chemistry·I L UrbatschA E Senior
Jan 1, 1993·Annual Review of Biochemistry·M M Gottesman, I Pastan
Dec 27, 1995·FEBS Letters·A E SeniorI L Urbatsch
Jan 19, 1996·The Journal of Biological Chemistry·U A GermannM M Gottesman
May 1, 1997·Archives of Biochemistry and Biophysics·B SankaranA E Senior
Oct 6, 1997·Proceedings of the National Academy of Sciences of the United States of America·S DeyS V Ambudkar
Feb 7, 1998·The Biochemical Journal·G WangJ T Zhang
Aug 26, 1998·Methods in Enzymology·A E SeniorI L Urbatsch
Aug 26, 1998·European Journal of Biochemistry·G WangJ T Zhang
May 20, 1999·Annual Review of Pharmacology and Toxicology·S V AmbudkarM M Gottesman
Oct 21, 1999·Biochemistry·C A HrycynaM M Gottesman
Mar 16, 2000·Proceedings of the National Academy of Sciences of the United States of America·Z E Sauna, S V Ambudkar
Mar 14, 2002·Proceedings of the National Academy of Sciences of the United States of America·Tip W Loo, David M Clarke
Jun 11, 2002·The Journal of Biological Chemistry·Shanthy L Nuti, U Subrahmanyeswara Rao
Sep 12, 2002·The Journal of Biological Chemistry·Tip W Loo, David M Clarke
Oct 11, 2003·The Journal of Biological Chemistry·Marwan K Al-ShawiRobert A Figler
Oct 18, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Daniella R StenhamKenneth J Linton
Mar 31, 2004·Biochemistry·Hiroshi OmoteMarwan K Al-Shawi
Sep 29, 2004·Nature Structural & Molecular Biology·Christopher F Higgins, Kenneth J Linton

❮ Previous
Next ❯

Citations

May 3, 2014·Quarterly Reviews of Biophysics·Peter M Jones, Anthony M George
Dec 8, 2009·The FEBS Journal·Emily Crowley, Richard Callaghan
Jan 20, 2012·Molecular and Cellular Biochemistry·Ruma Dey GhoshSoumitra Kumar Choudhuri
Sep 15, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jingwei ZhangGuangji Wang
Mar 7, 2014·The FEBS Journal·Jessica H van WonderenRichard Callaghan
Jan 24, 2007·Molecular Cancer Therapeutics·Zuben E Sauna, Suresh V Ambudkar
Jan 9, 2007·Pharmacology & Therapeutics·Christopher A McDevitt, Richard Callaghan

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.