Do drug substrates enter the common drug-binding pocket of P-glycoprotein through "gates"?

Biochemical and Biophysical Research Communications

Volumn 329, Issue 2, 2005, Pages 419-422

  Loo, Tip W ^a   Clarke, David M ^a  

^a NONE

Author keywords

Common drug binding pocket; Cysteine scanning mutagenesis; Disulfide cross linking; Gates; P glycoprotein; Thiol reactive analogues

Indexed keywords

CYSTEINE; GLYCOPROTEIN P;

DRUG BINDING; DRUG BINDING SITE; ENZYME ACTIVITY; LIPID BILAYER; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN EXPRESSION; REVIEW;

EID: 14644425991     PISSN: 0006291X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bbrc.2005.01.134     Document Type: Short Survey

References (25)

1. S.V. Ambudkar, S. Dey, C.A. Hrycyna, M. Ramachandra, I. Pastan, and M.M. Gottesman Biochemical, cellular, and pharmacological aspects of the multidrug transporter Annu. Rev. Pharmacol. Toxicol. 39 1999 361 398
2. F. Thiebaut, T. Tsuruo, H. Hamada, M.M. Gottesman, I. Pastan, and M.C. Willingham Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues Proc. Natl. Acad. Sci. USA 84 1987 7735 7738
3. A.H. Schinkel, J.J. Smit, O. van Tellingen, J.H. Beijnen, E. Wagenaar, L. van Deemter, C.A. Mol, M.A. van der Valk, E.C. Robanus-Maandag, H.P. te Riele, A.J.M. Berns, and P. Borst Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs Cell 77 1994 491 502
4. T.W. Loo, and D.M. Clarke Molecular dissection of the human multidrug resistance P-glycoprotein Biochem. Cell. Biol. 77 1999 11 23
5. C.G. Lee, M.M. Gottesman, C.O. Cardarelli, M. Ramachandra, K.T. Jeang, S.V. Ambudkar, I. Pastan, and S. Dey HIV-1 protease inhibitors are substrates for the MDR1 multidrug transporter Biochemistry 37 1998 3594 3601
6. M. Dean, A. Rzhetsky, and R. Allikmets The human ATP-binding cassette (ABC) transporter superfamily Genome Res. 11 2001 1156 1166
7. C.J. Chen, J.E. Chin, K. Ueda, D.P. Clark, I. Pastan, M.M. Gottesman, and I.B. Roninson Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells Cell 47 1986 381 389
8. T.W. Loo, and D.M. Clarke Identification of residues in the drug-binding site of human P-glycoprotein using a thiol-reactive substrate J. Biol. Chem. 272 1997 31945 31948
9. T.W. Loo, and D.M. Clarke Identification of residues in the drug-binding domain of human P-glycoprotein: Analysis of transmembrane segment 11 by cysteine-scanning mutagenesis and inhibition by dibromobimane J. Biol. Chem. 274 1999 35388 35392
10. T.W. Loo, and D.M. Clarke Identification of residues within the drug-binding domain of the human multidrug resistance P-glycoprotein by cysteine-scanning mutagenesis and reaction with dibromobimane J. Biol. Chem. 275 2000 39272 39278
11. T.W. Loo, and D.M. Clarke Defining the drug-binding site in the human multidrug resistance P-glycoprotein using MTS-verapamil J. Biol. Chem. 276 2001 14972 14979
12. T.W. Loo, M.C. Bartlett, and D.M. Clarke Permanent activation of the human P-glycoprotein by covalent modification of a residue in the drug-binding site J. Biol. Chem. 278 2003 20449 20452
13. T.W. Loo, and D.M. Clarke Location of the rhodamine-binding site in the human multidrug resistance P-glycoprotein J. Biol. Chem. 277 2002 44332 44338
14. T.W. Loo, M.C. Bartlett, and D.M. Clarke Methanethiosulfonate derivatives of rhodamine and verapamil activate human P-glycoprotein at different sites J. Biol. Chem. 278 2003 50136 50141
15. T.W. Loo, and D.M. Clarke The transmembrane domains of the human multidrug resistance P-glycoprotein are sufficient to mediate drug binding and trafficking to the cell surface J. Biol. Chem. 274 1999 24759 24765
16. T.W. Loo, M.C. Bartlett, and D.M. Clarke Simultaneous binding of two different drugs in the binding pocket of the human multidrug resistance P-glycoprotein J. Biol. Chem. 278 2003 39706 39710
17. T.W. Loo, M.C. Bartlett, and D.M. Clarke Substrate-induced conformational changes in the transmembrane segments of human P-glycoprotein. Direct evidence for the substrate-induced fit mechanism for drug binding J. Biol. Chem. 278 2003 13603 13606
18. T.W. Loo, and D.M. Clarke Determining the dimensions of the drug-binding domain of human P-glycoprotein using thiol cross-linkers as molecular rulers J. Biol. Chem. 276 2001 36877 36880
19. M.F. Rosenberg, R. Callaghan, R.C. Ford, and C.F. Higgins Structure of the multidrug resistance P-glycoprotein to 2.5 nm resolution determined by electron microscopy and image analysis J. Biol. Chem. 272 1997 10685 10694
20. T.W. Loo, M.C. Bartlett, and D.M. Clarke Disulfide cross-linking analysis shows that transmembrane segments 5 and 8 of human P-glycoprotein are close together on the cytoplasmic side of the membrane J. Biol. Chem. 279 2004 7692 7697
21. T.W. Loo, M.C. Bartlett, and D.M. Clarke Residues V133 and C137 in transmembrane segment 2 are close to residues A935 and G939 in transmembrane segment 11 of human P-glycoprotein J. Biol. Chem. 279 2004 18232 18238
22. T.W. Loo, M.C. Bartlett, and D.M. Clarke The drug-binding pocket of the human multidrug resistance P-glycoprotein is accessible to the aqueous medium Biochemistry 43 2004 12081 12089
23. Y. Raviv, H.B. Pollard, E.P. Bruggemann, I. Pastan, and M.M. Gottesman Photosensitized labeling of a functional multidrug transporter in living drug-resistant tumor cells J. Biol. Chem. 265 1990 3975 3980
24. L. Homolya, Z. Hollo, U.A. Germann, I. Pastan, M.M. Gottesman, and B. Sarkadi Fluorescent cellular indicators are extruded by the multidrug resistance protein J. Biol. Chem. 268 1993 21493 21496
25. C.F. Higgins, and M.M. Gottesman Is the multidrug transporter a flippase? Trends Biochem. Sci. 17 1992 18 21