The ABC Transporters: Structural Insights into Drug Transport

Transporters as Drug Carriers: Structure, Function, Substrates

Volumn 44, Issue , 2009, Pages 1-48

  Ford, Robert C ^a   Kamis, Alhaji B ^a   Kerr, Ian D ^b   Callaghan, Richard ^c  

^a UNIVERSITY OF MANCHESTER   (United Kingdom)

^b UNIVERSITY OF NOTTINGHAM   (United Kingdom)

^c UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

ABC protein; Electron microscopy; Multidrug resistance; Structural proteomics; Transporter

Indexed keywords

ELECTRON MICROSCOPY;

ABC TRANSPORTER; DRUG TRANSPORT; MULTIDRUG RESISTANCE; PROTEOMICS; STRUCTURAL INSIGHTS; TRANSPORTER;

MOLECULAR BIOLOGY;

EID: 85018617661     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9783527627424.ch1     Document Type: Chapter

References (250)

1. Klein, I., Sarkadi, B., and Varadi, A. (1999) An inventory of the human ABC proteins. Biochimica et Biophysica Acta, 1461 (2), 237-262.
2. Linton, K.J. and Higgins, C.F. (1998) The Escherichia coli ATP-binding cassette (ABC) proteins. Molecular Microbiology, 28 (1), 5-13.
3. Rosenberg, M.F., Mao, Q., Holzenburg, A., Ford, R.C., Deeley, R.G., and Cole, S.P. (2001) The structure of the multidrug resistance protein 1 (MRP1/ABCC1). Crystallization and single-particle analysis. The Journal of Biological Chemistry, 276 (19), 16076-16082.
4. Higgins, C.F. (1992) ABC transporters: from microorganisms to man. Annual Review of Cell Biology, 8, 67-113.
5. Childs, S. and Ling, V. (1994) The MDR superfamily of genes and its biological implications, in Important Advances in Oncology (eds V.T. DeVita, S. Hellman, and S.A. Rosenberg), Lippincott, Philadelphia, PA, pp. 21-36.
6. Dean, M. and Allikmets, R. (1995) Evolution of ATP-binding cassette transporter genes. Current Opinion in Genetics & Development, 5 (6), 779-785.
7. Dean, M., Rzhetsky, A., and Allikmets, R. (2001) The human ATP-binding cassette (ABC) transporter superfamily. Genome Research, 11 (7), 1156-1166.
8. Mutch, D.M., Anderle, P., Fiaux, M., Mansourian, R., Vidal, K., Wahli, W., Williamson, G., and Roberts, M.A. (2004) Regional variations in ABC transporter expression along the mouse intestinal tract. Physiological Genomics, 17 (1), 11-20.
9. Kerr, I.D. (2002) Structureandassociation of ATP-binding cassette transporter nucleotide-binding domains. Biochimica et Biophysica Acta, 1561 (1), 47-64.
10. Hosie, A.H., Allaway, D., Jones, M.A., Walshaw, D.L., Johnston, A.W., and Poole, P.S. (2001) Solute-binding protein-dependent ABC transporters are responsible for solute efflux in addition to solute uptake. Molecular Microbiology, 40, 1449-1459.
11. Kast, C., Canfield, V., Levenson, R., and Gros, P. (1995) Membrane topology of P-glycoprotein as determined by epitope insertion: transmembrane organization of the N-terminal domain of mdr3. Biochemistry, 34 (13), 4402-4411.
12. Kast, C., Canfield, V., Levenson, R., and Gros, P. (1996) Transmembrane organization of mouse P-glycoprotein determined by epitope insertion and immunofluorescence. The Journal of Biological Chemistry, 271 (16), 9240-9248.
13. Tusnady, G.E., Bakos, E., Varadi, A., and Sarkadi, B. (1997) Membrane topology distinguishes a subfamily of the ATP-binding cassette (ABC) transporters. FEBS Letters, 402 (1), 1-3.
14. Jha, S., Karnani, N., Dhar, S.K., Mukhopadhayay, K., Shukla, S., Saini, P., Mukhopadhayay, G., and Prasad, R. (2003) Purification and characterization ofthe N-terminal nucleotide binding domain of an ABC drug transporter of Candida albicans: uncommon cysteine 193 of Walker A is critical for ATP hydrolysis. Biochemistry, 42 (36), 10822-10832.
15. Locher, K.P. and Borths, E. (2004) ABC transporter architecture and mechanism: implications fromthe crystal structures of BtuCD and BtuF. FEBS Letters, 564 (3), 264-268.
16. Azzaria, M., Schurr, E., and Gros, P. (1989) Discrete mutations introduced in the predicted nucleotide-binding sites of the mdr1 gene abolish its ability to confer multidrug resistance. Molecular and Cellular Biology, 9 (12), 5289-5297.
17. Al-Shawi, M.K. and Senior, A.E. (1993) Characterization of the adenosine triphosphatase activity of Chinese hamster P-glycoprotein. The Journal of Biological Chemistry, 268 (6), 4197-4206.
18. Gao, M., Cui, H.R., Loe, D.W., Grant, C.E., Almquist, K.C., Cole, S.P., and Deeley, R.G. (2000) Comparison ofthe functional characteristics of the nucleotide binding domains ofmultidrug resistance protein 1. The Journal of Biological Chemistry, 275 (17), 13098-13108.
19. Hou, Y., Cui, L., Riordan, J.R., and Chang, X. (2000) Allosteric interactions between the two non-equivalent nucleotide binding domains ofmultidrug resistance protein MRP1. The Journal of Biological Chemistry, 275 (27), 20280-20287.
20. Lapinski, P.E., Neubig, R.R., and Raghavan, M. (2001) Walker A lysine mutations of TAP1 and TAP2 interfere with peptide translocation but not peptide binding. The Journal of Biological Chemistry, 276 (10), 7526-7533.
21. Saveanu, L., Daniel, S., and van Endert, P.M. (2001) Distinct functions of the ATP binding cassettes oftransporters associated with antigen processing: a mutational analysis of Walker A and B sequences. The Journal of Biological Chemistry, 276 (25), 22107-22113.
22. Proff, C. and Kolling, R. (2001) Functional asymmetry ofthe two nucleotide binding domains in the ABC transporter Ste6. Molecular & General Genetics, 264 (6), 883-893.
23. Anderson, M.P. and Welsh, M.J. (1992) Regulation by ATP and ADP of CFTR chloride channels that contain mutant nucleotide-binding domains. Science, 257 (5077), 1701-1704.
24. Carson, M.R., Travis, S.M., and Welsh, M.J. (1995) The two nucleotide-binding domains of cystic fibrosis transmembrane conductance regulator (CFTR) have distinct functions in controlling channel activity. The Journal of Biological Chemistry, 270 (4), 1711-1717.
25. Cui, L., Aleksandrov, L., Chang, X.B., Hou, Y.X., He, L., Hegedus, T., Gentzsch, M., Aleksandrov, A., Balch, W.E., and Riordan, J.R. (2007) Domain interdependence in the biosynthetic assembly of CFTR. Journal of Molecular Biology, 365, 981-994.
26. Senior, A.E., al-Shawi, M.K., and Urbatsch, I.L. (1995) ATP hydrolysis by multidrug-resistance protein from Chinese hamster ovary cells. Journal of Bioenergetics and Biomembranes, 27 (1), 31-36.
27. Szakacs, G., Ozvegy, C., Bakos, E., Sarkadi, B., and Varadi, A. (2001) Role ofglycine-534 and glycine-1179 of human multidrug resistance protein (MDR1) in drug-mediated control of ATP hydrolysis. The Biochemical Journal, 356 (Pt 1), 71-75.
28. Urbatsch, I.L., Gimi, K., Wilke-Mounts, S., and Senior, A.E. (2000) Conserved Walker A Ser residues in the catalytic sites of P-glycoprotein are critical for catalysis and involved primarily at the transition state step. The Journal of Biological Chemistry, 275 (32), 25031-25038.
29. Urbatsch, I.L., Gimi, K., Wilke-Mounts, S., and Senior, A.E. (2000) Investigation of the role of glutamine-471 and glutamine-1114 in the two catalytic sites of P-glycoprotein. Biochemistry, 39 (39), 11921-11927.
30. Takada, Y., Yamada, K., Taguchi, Y., Kino, K., Matsuo, M., Tucker, S.J., Komano, T., Amachi, T., and Ueda, K. (1998) Nonequivalent cooperation between the two nucleotide-binding folds of P-glycoprotein. Biochimica et Biophysica Acta, 1373 (1), 131-136.
31. Loo, T.W. and Clarke, D.M. (1995) Covalent modification of human P-glycoprotein mutants containing a single cysteine in either nucleotidebinding fold abolishes drug-stimulated ATPase activity. The Journal of Biological Chemistry, 270 (39), 22957-22961.
32. Hrycyna, C.A., Ramachandra, M., Germann, U.A., Cheng, P.W., Pastan, I., and Gottesman, M.M. (1999) Both ATP sites of human P-glycoprotein are essential but not symmetric. Biochemistry, 38 (42), 13887-13899.
33. Vigano, C., Julien, M., Carrier, I., Gros, P., and Ruysschaert, J.M. (2002) Structural and functional asymmetry of the nucleotide-binding domains of P-glycoprotein investigated by attenuated total reflection Fourier transform infrared spectroscopy. The Journal of Biological Chemistry, 277 (7), 5008-5016.
34. Berridge, G., Walker, J.A., Callaghan, R., and Kerr, I.D. (2003) The nucleotidebinding domains of P-glycoprotein. Functional symmetry in the isolated domain demonstrated by N-ethylmaleimide labelling. European Journal of Biochemistry, 270 (7), 1483-1492.
35. Walker, J.E., Saraste, M., Runswick, M.J., and Gay, N.J. (1982) Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold. The EMBOJournal, 1 (8), 945-951.
36. Young, J. and Holland, I.B. (1999) ABC transporters: bacterial exporters-revisited five years on. Biochimica et Biophysica Acta, 1461 (2), 177-200.
37. Diederichs, K., Diez, J., Greller, G., Muller, C., Breed, J., Schnell, C., Vonrhein, C., Boos, W., and Welte, W. (2000) Crystal structure of MalK, the ATPase subunit of the trehalose/maltose ABC transporter of the archaeon Thermococcus litoralis. The EMBO Journal, 19 (22), 5951-5961.
38. Ambudkar, S.V., Kim, I.W., Xia, D., and Sauna, Z.E. (2006) The A-loop, a novel conserved aromatic acid subdomain upstream of the Walker A motif in ABC transporters, is critical for ATP binding. FEBS Letters, 580, 1049-1055.
39. Holland, I.B. and Blight, M.A. (1999) ABC-ATPases, adaptable energy generators fuelling transmembrane movement of a variety of molecules in organisms from bacteria to humans. Journal of Molecular Biology, 293 (2), 381-399.
40. Martin, C., Berridge, G., Higgins, C.F., Mistry, P., Charlton, P., and Callaghan, R. (2000) Communication between multiple drug binding sites on P-glycoprotein. Molecular Pharmacology, 58, 624-632.
41. Saurin, W., Hofnung, M., and Dassa, E. (1999) Getting in or out: early segregation between importers and exporters in the evolution of ATP-binding cassette (ABC) transporters. Journal of Molecular Evolution, 48 (1), 22-41.
42. Locher, K.P., Lee, A.T., and Rees, D.C. (2002) The E. coli BtuCD structure: a framework for ABC transporter architecture and mechanism. Science, 296 (5570), 1091-1098.
43. Pinkett, H.W., Lee, A.T., Lum, P., Locher, K.P., and Rees, D.C. (2007) An inwardfacing conformation of a putative metal-chelate-type ABC transporter. Science, 315, 373-377.
44. Reyes, C.L. and Chang, G. (2005) Structure of the ABC transporter MsbA in complex with ADP-vanadate and lipopolysaccharide. Science, 308, 1028-1031.
45. Retraction in: Chang, G., Roth, C.B., Reyes, C.L., Pornillos, O., Chen, Y.J., and Chen, A.P. (2006) Science, 314, 1875.
46. Chang, G. (2007) Retraction of "Structure of MsbA from Vibrio cholera: a multidrug resistance ABC transporter homolog in a closedconformation" [J. Mol. Biol. (2003) 330: 419-430]. Journal of Molecular Biology, 369, 596.
47. Chang, G., Roth, C.B., Reyes, C.L., Pornillos, O., Chen, Y.J., and Chen, A.P. (2006) Retraction. Science, 314, 1875.
48. Ward, A., Reyes, C.L., Yu, J., Roth, C.B., and Chang, G. (2007) Flexibility in the ABC transporter MsbA: alternating access with a twist. Proceedings ofthe National Academy of Sciences of the United States of America, 104, 19005-19010.
49. Oldham, M.L., Khare, D., Quiocho, F.A., Davidson, A.L., and Chen, J. (2007) Crystal structure of a catalytic intermediate of the maltose transporter. Nature, 450, 515-521.
50. Rosenberg, M.F., Callaghan, R., Ford, R.C., and Higgins, C.F. (1997) Structure of the multidrug resistance P-glycoprotein to 2.5 nm resolution determined by electron microscopy and image analysis. The Journal of Biological Chemistry, 272 (16), 10685-10694.
51. Rosenberg, M.F., Velarde, G., Ford, R.C., Martin, C., Berridge, G., Kerr, I.D., Callaghan, R., Schmidlin, A., Wooding, C., Linton, K.J., and Higgins, C.F. (2001) Repacking of the transmembrane domains of P-glycoprotein during the transport ATPase cycle. The EMBO Journal, 20 (20), 5615-5625.
52. Rosenberg, M.F., Kamis, A.B., Aleksandrov, L.A., Ford, R.C., and Riordan, J.R. (2004) Purification and crystallization of the cystic fibrosis transmembrane conductance regulator (CFTR). The Journal of Biological Chemistry, 279, 39051-39057.
53. Dey, S., Ramachandra, M., Pastan, I., Gottesman, M.M., and Ambudkar, S.V. (1997) Evidence for two nonidentical drug-interaction sites in the human P-glycoprotein. Proceedings of the National Academy of Sciences of the United States of America, 94 (20), 10594-10599.
54. Loo, T.W. and Clarke, D.M. (2001) Defining the drug-binding site in the human multidrug resistance P-glycoprotein using a methanethiosulfonate analog of verapamil, MTS-verapamil. The Journal of Biological Chemistry, 276, 14972-14979.
55. Loo, T.W. and Clarke, D.M. (2001) Determining the dimensions ofthe drug-binding domain ofhuman P-glycoprotein using thiol cross-linking compounds as molecular rulers. The Journal of Biological Chemistry, 276, 36877-36880.
56. Loo, T.W. and Clarke, D.M. (2002) Vanadate trapping of nucleotide at the ATP-binding sites of human multidrug resistance P-glycoprotein exposes different residues to the drug-binding site. Proceedings ofthe National Academy of Sciences of the United States of America, 99 (6), 3511-3516.
57. Loo, T.W. and Clarke, D.M. (2002) Location ofthe rhodamine-binding site in the human multidrug resistance P-glycoprotein. The Journal of Biological Chemistry, 277 (46), 44332-44338.
58. Loo, T.W., Bartlett, M.C., and Clarke, D.M. (2003) Substrate-induced conformational changes in the transmembrane segments ofhuman P-glycoprotein. Direct evidence for the substrate-induced fit mechanism for drug binding. The Journal of Biological Chemistry, 278 (16), 13603-13606.
59. Loo, T.W., Bartlett, M.C., and Clarke, D.M. (2003) Simultaneous binding of two different drugs in the binding pocket of the human multidrug resistance P-glycoprotein. The Journal of Biological Chemistry, 278 (41), 39706-39710.
60. Shapiro, A.B., Fox, K., Lam, P., and Ling, V. (1999) Stimulation of P-glycoprotein-mediated drug transport by prazosin and progesterone. Evidence for a third drugbinding site. European Journal of Biochemistry, 259, 841-850.
61. Martin, C., Berridge, G., Mistry, P., Higgins, C., Charlton, P., and Callaghan, R. (1999) The molecular interaction ofthe high affinity reversal agent XR9576 with P-glycoprotein. British Journal of Pharmacology, 128 (2), 403-411.
62. Schmitt, L. and Tampe, R. (2002) Structure and mechanism of ABC transporters. Current Opinion in Structural Biology, 12 (6), 754-760.
63. Hung, L.W., Wang, I.X., Nikaido, K., Liu, P.Q., Ames, G.F., and Kim, S.H. (1998) Crystal structure of the ATP-binding subunit of an ABC transporter. Nature, 396 (6712), 703-707.
64. Hopfner, K.P., Karcher, A., Shin, D.S., Craig, L., Arthur, L.M., Carney, J.P., and Tainer, J.A. (2000) Structural biology of Rad50 ATPase: ATP-driven conformational control in DNA doublestrand break repair and the ABC-ATPase superfamily. Cell, 101 (7), 789-800.
65. Gadsby, D.C., Vergani, P., and Csanady, L. (2006) The ABC protein turned chloride channel whose failure causes cystic fibrosis. Nature, 440, 477-483.
66. Moody, J.E., Millen, L., Binns, D., Hunt, J.F., and Thomas, P.J. (2002) Cooperative, ATP-dependent association of the nucleotide binding cassettes during the catalytic cycle of ATP-binding cassette transporters. The Journal of Biological Chemistry, 277 (24), 21111-21114.
67. Qian, Y.M., Qiu, W., Gao, M., Westlake, C.J., Cole, S.P., and Deeley, R.G. (2001) Characterization of binding of leukotriene C4 by human multidrug resistance protein 1: evidence of differential interactions with NH2- and COOH-proximal halves of the protein. The Journal of Biological Chemistry, 276 (42), 38636-38644.
68. Hou, Y.X., Cui, L., Riordan, J.R., and Chang, X.B. (2002) ATP binding to the first nucleotide-binding domain of multidrug resistance protein MRP1 increases binding and hydrolysis of ATP and trapping of ADP at the second domain. The Journal of Biological Chemistry, 277 (7), 5110-5119.
69. - channel. The Journal of General Physiology, 119 (6), 545-559.
70. Aleksandrov, L., Aleksandrov, A.A., Chang, X.B., and Riordan, J.R. (2002) The first nucleotide binding domain of cystic fibrosis transmembrane conductance regulator is a site of stable nucleotide interaction, whereas the second is a site of rapid turnover. The Journal of Biological Chemistry, 277 (18), 15419-15425.
71. vanVeen, H.W., Margolles, A., Muller, M., Higgins, C.F., and Konings, W.N. (2000) The homodimeric ATP-binding cassette transporter LmrA mediates multidrug transport by an alternating two-site (two-cylinder engine) mechanism. The EMBO Journal, 19 (11), 2503-2514.
72. van Veen, H.W., Margolles, A., Putman, M., Sakamoto, K., and Konings, W.N. (1999) Multidrug resistance in lactic acid bacteria: molecular mechanisms and clinical relevance. Antonie van Leeuwenhoek, 76 (1-4), 347-352.
73. van Veen, H.W., Putman, M., Margolles, A., Sakamoto, K., and Konings, W.N. (1999) Structure-function analysis of multidrug transporters in Lactococcus lactis. Biochimica et Biophysica Acta, 1461 (2), 201-206.
74. vanVeen, H.W. and Konings, W.N. (1996) Multidrug resistance mediated by a bacterial homolog of the human multidrug transporter MDR1. Proceedings ofthe National Academy of Sciences ofthe United States of America, 93 (20), 10668-10672.
75. Shepard, R.L., Winter, M.A., Hsaio, S.C., Pearce, H.L., Beck, W.T., and Dantzig, A.H. (1998) Effect of modulators on the ATPase activity and vanadate nucleotide trapping of human P-glycoprotein. Biochemical Pharmacology, 56 (6), 719-727.
76. Sauna, Z.E. and Ambudkar, S.V. (2000) Evidence for a requirement for ATP hydrolysis at two distinct steps during a single turnover of the catalytic cycle of human P-glycoprotein. Proceedings of the National Academy of Sciences of the United States of America, 97 (6), 2515-2520.
77. Kerr, K.M., Sauna, Z.E., and Ambudkar, S.V. (2001) Correlation between steady-state ATP hydrolysis and vanadate-induced ADP trapping in human P-glycoprotein. Evidence for ADP release as the rate-limiting step in the catalytic cycle and its modulation by substrates. The Journal of Biological Chemistry, 276 (12), 8657-8664.
78. Sauna, Z.E. and Ambudkar, S.V. (2001) Characterization of the catalytic cycle of ATP hydrolysis by human P-glycoprotein. The two ATP hydrolysis events in a single catalytic cycle are kinetically similar but affect different functional outcomes. The Journal of Biological Chemistry, 276 (15), 11653-11661.
79. 32P] diphosphate-trapped transition state intermediates of human P-glycoprotein are generated in the absence and presence of ATP hydrolysis. The Journal of Biological Chemistry, 276 (24), 21199-21208.
80. Sauna, Z.E., Smith, M.M., Muller, M., and Ambudkar, S.V. (2001) Evidence for the vectorial nature of drug (substrate)-stimulated ATP hydrolysis by human P-glycoprotein. The Journal of Biological Chemistry, 276 (36), 33301-33304.
81. Martin, C., Higgins, C.F., and Callaghan, R. (2001) The vinblastine binding site adopts high- and low-affinity conformations during a transport cycle of P-glycoprotein. Biochemistry, 40 (51), 15733-15742.
82. Davidson, A.L. and Chen, J. (2004) ATP-binding cassette transporters in bacteria. Annual Review of Biochemistry, 73, 241-268.
83. Borges-Walmsley, M.I., McKeegan, K.S., and Walmsley, A.R. (2003) Structure and function of efflux pumps that confer resistance to drugs. The Biochemical Journal, 376 (Pt 2), 313-338.
84. Loo, T.W., Bartlett, M.C., and Clarke, D.M. (2002) The "LSGGQ" motif in each nucleotide-binding domain ofhuman P-glycoprotein is adjacent to the opposing Walker A sequence. The Journal of Biological Chemistry, 277 (44), 41303-41306.
85. Loo, T.W., Bartlett, M.C., and Clarke, D.M. (2003) Drug binding in human P-glycoprotein causes conformational changes in both nucleotide-binding domains. The Journal of Biological Chemistry, 278 (3), 1575-1578.
86. Callaghan, R., Ford, R.C., and Kerr, I.D. (2006) The translocation mechanism of P-glycoprotein. FEBS Letters, 580, 1056-1063.
87. Schneider, E. and Hunke, S. (1998) ATP-binding-cassette (ABC) transport systems: functional and structural aspects of the ATP-hydrolyzing subunits/domains. FEMS Microbiology Reviews, 22 (1), 1-20.
88. Yuan, Y.R., Blecker, S., Martsinkevich, O., Millen, L., Thomas, P.J., and Hunt, J.F. (2001) The crystal structure ofthe MJ0796 ATP-binding cassette. Implications for the structural consequences of ATP hydrolysis in the active site of an ABC transporter. The Journal of Biological Chemistry, 276 (34), 32313-32321.
89. Chen, H.L., Gabrilovich, D., Tampe, R., Girgis, K.R., Nadaf, S., and Carbone, D.P. (1996) A functionally defective allele of TAP1 results in loss of MHC class I antigen presentation in a human lung cancer. Nature Genetics, 13 (2), 210-213.
90. Riordan, J.R. (1993) The cystic fibrosis transmembrane conductance regulator. Annual Review of Physiology, 55, 609-630.
91. Dawson, R.J. and Locher, K.P. (2006) Structure of a bacterial multidrug ABC transporter. Nature, 443, 180-185.
92. Murakami, S., Nakashima, R., Yamashita, E., and Yamaguchi, A. (2002) Crystal structure of bacterial multidrug efflux transporter AcrB. Nature, 419 (6907), 587-593.
93. Koronakis, V., Sharff, A., Koronakis, E., Luisi, B., and Hughes, C. (2000) Crystal structure of the bacterial membrane protein TolC central to multidrug efflux and protein export. Nature, 405 (6789), 914-919.
94. Chang, G. (2003) Structure of MsbA from Vibrio cholera: a multidrug resistance ABC transporter homolog in a closed conformation. Journal of Molecular Biology, 330 (2), 419-430.
95. Chang, G. and Roth, C.B. (2001) Structure of MsbA from E. coli: a homolog of the multidrug resistance ATP binding cassette (ABC) transporters. Science, 293 (5536), 1793-1800.
96. Faham, S. and Bowie, J.U. (2002) Bicelle crystallization: a new method for crystallizing membrane proteins yields a monomeric bacteriorhodopsin structure. Journal of Molecular Biology, 316 (1), 1-6.
97. Nollert, P., Navarro, J., and Landau, E.M. (2002) Crystallization of membrane proteins in cubo. Methods in Enzymology, 343, 183-199.
98. Armstrong, S., Tabernero, L., Zhang, H., Hermodsen, M., and Stauffacher, C. (1998) Powering the ABC transporters: the 2.5 Å crystal structure of the ABC domain of RbsA. Pediatric Pulmonology, 17, 91-92.
99. Karpowich, N., Martsinkevich, O., Millen, L., Yuan, Y.R., Dai, P.L., MacVey, K., Thomas, P.J., and Hunt, J.F. (2001) Crystal structures of the MJ1267 ATP binding cassette reveal an induced-fit effect at the ATPase active site of an ABC transporter. Structure, 9 (7), 571-586.
100. Lowe, J., Cordell, S.C., and van den Ent, F. (2001) Crystal structure of the SMC head domain: an ABCAT Pase with 900 residues antiparallel coiled-coil inserted. Journal of Molecular Biology, 306 (1), 25-35.
101. Lamers, M.H., Perrakis, A., Enzlin, J.H., Winterwerp, H.H., de Wind, N., and Sixma, T.K. (2000) The crystal structure of DNA mismatch repair protein MutS binding to a G × T mismatch. Nature, 407 (6805), 711-717.
102. Obmolova, G., Ban, C., Hsieh, P., and Yang, W. (2000) Crystal structures of mismatch repair protein MutS and its complex with a substrate DNA. Nature, 407 (6805), 703-710.
103. Gaudet, R. and Wiley, D.C. (2001) Structure of the ABC ATPase domain of human TAP1, the transporter associated with antigen processing. The EMBO Journal, 20 (17), 4964-4972.
104. Verdon, G., Albers, S.V., Dijkstra, B.W., Driessen, A.J., and Thunnissen, A.M. (2003) Crystal structures of the ATPase subunit of the glucose ABC transporter from Sulfolobus solfataricus: nucleotide-free and nucleotide-bound conformations. Journal of Molecular Biology, 330 (2), 343-358.
105. Schmitt, L., Benabdelhak, H., Blight, M.A., Holland, I.B., and Stubbs, M.T. (2003) Crystal structure ofthe nucleotidebinding domain of the ABC-transporter haemolysin B: identification of a variable region within ABC helical domains. Journal of Molecular Biology, 330 (2), 333-342.
106. Lewis, H.A., Buchanan, S.G., Burley, S.K., Conners, K., Dickey, M., Dorwart, M., Fowler, R., Gao, X., Guggino, W.B., Hendrickson, W.A., Hunt, J.F., Kearins, M.C., Lorimer, D., Maloney, P.C., Post, K.W., Rajashankar, K.R., Rutter, M.E., Sauder, J.M., Shriver, S., Thibodeau, P.H., Thomas, P.J., Zhang, M., Zhao, X., and Emtage, S. (2004) Structure of nucleotide-binding domain 1 of the cystic fibrosis transmembrane conductance regulator. The EMBOJournal, 23 (2), 282-293.
107. McKeegan, K.S., Borges-Walmsley, M.I., and Walmsley, A.R. (2003) The structure and function of drug pumps: an update. Trends in Microbiology, 11 (1), 21-29.
108. Davidson, A.L., Laghaeian, S.S., and Mannering, D.E. (1996) The maltose transport system of Escherichia coli displays positive cooperativity in ATP hydrolysis. The Journal of Biological Chemistry, 271 (9), 4858-4863.
109. Liu, C.E., Liu, P.Q., and Ames, G.F. (1997) Characterization of the adenosine triphosphatase activity of the periplasmic histidine permease, a traffic ATPase (ABC transporter). The Journal of Biological Chemistry, 272 (35), 21883-21891.
110. Stenham, D.R., Campbell, J.D., Sansom, M.S., Higgins, C.F., Kerr, I.D., and Linton, K.J. (2003) Anatomicdetailmodel for the human ATP binding cassette transporter P-glycoprotein derived from disulfide cross-linking and homology modelling. The FASEB Journal, 17 (15), 2287-2289.
111. Rosenberg, M.F., Callaghan, R., Modok, S., Higgins, C.F., and Ford, R.C. (2005) 3-D structure of P-glycoprotein: the transmembrane regions adopt an asymmetric configuration in the nucleotide-bound state. The Journal of Biological Chemistry, 280, 2857-2862.
112. Hollenstein, K., Frei, D.C., and Locher, K.P. (2007) Structure of an ABC transporter in complex with its binding protein. Nature, 446, 213-216.
113. McDevitt, C.A., Collins, R.F., Conway, M., Modok, S., Storm, J., Kerr, I.D., Ford, R.C., and Callaghan, R. (2006) Purification and 3D structural analysis of oligomeric human multidrug transporter ABCG2. Structure, 11, 1623-1632.
114. Awayn, N.H., Rosenberg, M.F., Kamis, A.B., Aleksandrov, L.A., Riordan, J.R., and Ford, R.C. (2005) Crystallographic and single-particle analyses of native-and nucleotide-bound forms of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Biochemical Society Transactions, 33, 996-999.
115. Rosenberg, M.F., Kamis, A.B., Callaghan, R. , Higgins, C.F., and Ford, R.C. (2003) Three-dimensional structures of the mammalian multidrug resistance P-glycoprotein demonstrate major conformational changes in the transmembrane domains upon nucleotide binding. The Journal of Biological Chemistry, 278, 8294-8299.
116. Chami, M., Steinfels, E., Orelle, C., Jault, J.M., Di Pietro, A., Rigaud, J.L., and Marco, S. (2002) Three-dimensional structure by cryo-electron microscopy of YvcC, an homodimeric ATP-binding cassette transporter from Bacillus subtilis. Journal of Molecular Biology, 315 (5), 1075-1085.
117. Ferreira-Pereira, A., Marco, S., Decottignies, A., Nader, J., Goffeau, A., and Rigaud, J.L. (2003) Threedimensional reconstruction of the Saccharomyces cerevisiae multidrug resistance protein PdrSp. The Journal of Biological Chemistry, 278 (14), 11995-11999.
118. Kamis, A.B. (2005) Purification and electron microscopic studies of two ABC transporter proteins of clinical relevance. PhD thesis. University of Manchester, UK.
119. Mikhailov, M.V., Campbell, J.D., de Wet, H., Shimomura, K., Zadek, B., Collins, R.F., Sansom, M.S., Ford, R.C., and Ashcroft, F.M. (2005) 3-D structural and functional characterization ofthe purified KATP channel complex Kir6.2-SUR1. The EMBOJournal, 24, 4166-4175.
120. Hofacker, M., Gompf, S., Zutz, A., Presenti, C., Haase, W., van der Does, C., Model, K., and Tampe, R. (2007) Structural and functional fingerprint of the mitochondrial ATP-binding cassette transporter Mdl1 from Saccharomyces cerevisiae. The Journal of Biological Chemistry, 282, 3951-3961.
121. Higgins, C.F. (2007) Multiple molecular mechanisms for multidrug resistance transporters. Nature, 446, 749-757.
122. Lage, H. (2003) ABC-transporters: implications on drug resistance from microorganisms to human cancers. International Journal of Antimicrobial Agents, 22 (3), 188-199.
123. Borst, P., Balzarini, J., Ono, N., Reid, G., de Vries, H., Wielinga, P., Wijnholds, J., and Zelcer, N. (2004) The potential impact of drug transporters on nucleoside-analog-based antiviral chemotherapy. Antiviral Research, 62 (1), 1-7.
124. Biedler, J.L. and Riehm, H. (1970) Cellular resistance to actinomycin D in Chinese hamster cells in vitro: cross-resistance, radioautographic, and cytogenetic studies. Cancer Research, 30 (4), 1174-1184.
125. Gottesman, M.M., Fojo, T., and Bates, S.E. (2002) Multidrug resistance in cancer: role of ATP-dependent transporters. Nature Reviews. Cancer, 2 (1), 48-58.
126. Van Bambeke, F., Balzi, E., and Tulkens, P.M. (2000) Antibiotic efflux pumps. Biochemical Pharmacology, 60 (4), 457-470.
127. Paulsen, I.T., Brown, M.H., and Skurray, R. A. (1996) Proton-dependent multidrug efflux systems. Microbiological Reviews, 60 (4), 575-608.
128. van Veen, H.W. and Konings, W.N. (1998) The ABC family ofmultidrug transporters in microorganisms. Biochimica et Biophysica Acta, 1365 (1-2), 31-36.
129. Lander, E.S., Linton, L.M., Birren, B., Nusbaum, C., Zody, M.C., Baldwin, J., Devon, K., Dewar, K., Doyle, M., FitzHugh, W., Funke, R., Gage, D., Harris, K., Heaford, A., Howland, J., Kann, L., Lehoczky, J., LeVine, R., McEwan, P., McKernan, K., Meldrim, J., Mesirov, J.P., Miranda, C., Morris, W., Naylor, J., Raymond, C., Rosetti, M., Santos, R., Sheridan, A., Sougnez, C., Stange-Thomann, N., Stojanovic, N., Subramanian, A., Wyman, D., Rogers, J., Sulston, J., Ainscough, R., Beck, S., Bentley, D., Burton, J., Clee, C., Carter, N., Coulson, A., Deadman, R., Deloukas, P., Dunham, A., Dunham, I., Durbin, R., French, L., Grafham, D., Gregory, S., Hubbard, T., Humphray, S., Hunt, A., Jones, M., Lloyd, C., McMurray, A., Matthews, L., Mercer, S., Milne, S., Mullikin, J.C., Mungall, A., Plumb, R., Ross, M., Shownkeen, R., Sims, S., Waterston, R.H., Wilson, R.K., Hillier, L.W., McPherson, J.D., Marra, M.A., Mardis, E.R., Fulton, L.A., Chinwalla, A.T., Pepin, K.H., Gish, W.R., Chissoe, S. L., Wendl, M.C., Delehaunty, K.D., Miner, T.L., Delehaunty, A., Kramer, J.B., Cook, L.L., Fulton, R.S., Johnson, D.L., Minx, P.J., Clifton, S.W., Hawkins, T., Branscomb, E., Predki, P., Richardson, P., Wenning, S., Slezak, T., Doggett, N., Cheng, J.F., Olsen, A., Lucas, S., Elkin, C., Uberbacher, E., Frazier, M., Gibbs, R.A., Muzny, D.M., Scherer, S.E., Bouck, J.B., Sodergren, E.J., Worley, K.C., Rives, C.M., Gorrell, J.H., Metzker, M.L., Naylor, S.L., Kucherlapati, R.S., Nelson, D.L., Weinstock, G.M., Sakaki, Y., Fujiyama, A., Hattori, M., Yada, T., Toyoda, A., Itoh, T., Kawagoe, C., Watanabe, H., Totoki, Y., Taylor, T., Weissenbach, J., Heilig, R., Saurin, W., Artiguenave, F., Brottier, P., Bruls, T., Pelletier, E., Robert, C., Wincker, P., Smith, D.R., Doucette-Stamm, L., Rubenfield, M., Weinstock, K., Lee, H.M., Dubois, J., Rosenthal, A., Platzer, M., Nyakatura, G., Taudien, S., Rump, A., Yang, H., Yu, J., Wang, J., Huang, G., Gu, J., Hood, L., Rowen, L., Madan, A., Qin, S., Davis, R.W., Federspiel, N.A., Abola, A.P., Proctor, M.J., Myers, R.M., Schmutz, J., Dickson, M., Grimwood, J., Cox, D.R., Olson, M.V., Kaul, R., Shimizu, N., Kawasaki, K., Minoshima, S., Evans, G.A., Athanasiou, M., Schultz, R., Roe, B.A., Chen, F., Pan, H., Ramser, J., Lehrach, H., Reinhardt, R., McCombie, W.R., de la Bastide, M., Dedhia, N., Blocker, H., Hornischer, K., Nordsiek, G., Agarwala, R., Aravind, L., Bailey, J.A., Bateman, A., Batzoglou, S., Birney, E., Bork, P., Brown, D.G., Burge, C. B., Cerutti, L., Chen, H.C., Church, D., Clamp, M., Copley, R.R., Doerks, T., Eddy, S.R., Eichler, E.E., Furey, T.S., Galagan, J., Gilbert, J.G., Harmon, C., Hayashizaki, Y., Haussler, D., Hermjakob, H., Hokamp, K., Jang, W., Johnson, L.S., Jones, T.A., Kasif, S., Kaspryzk, A., Kennedy, S., Kent, W.J., Kitts, P., Koonin, E.V., Korf, I., Kulp, D., Lancet, D. , Lowe, T.M., McLysaght, A., Mikkelsen, T., Moran, J.V., Mulder, N., Pollara, V.J., Ponting, C.P., Schuler, G., Schultz, J., Slater, G., Smit, A.F., Stupka, E., Szustakowski, J., Thierry-Mieg, D., Thierry-Mieg, J., Wagner, L., Wallis, J., Wheeler, R., Williams, A., Wolf, Y.I., Wolfe, K.H., Yang, S.P., Yeh, R.F., Collins, F., Guyer, M.S., Peterson, J., Felsenfeld, A., Wetterstrand, K.A., Patrinos, A., Morgan, M.J., Szustakowki, J., de Jong, P., Catanese, J.J., Osoegawa, K., Shizuya, H., Choi, S., and Chen, Y.J., (2001) Initial sequencing and analysis of the human genome. Nature, 409 (6822), 860-921.
130. Venter, J.C., Adams, M.D., Myers, E.W., Li, P.W., Mural, R.J., Sutton, G.G., Smith, H.O., Yandell, M., Evans, C.A., Holt, R.A., Gocayne, J.D., Amanatides, P., Ballew, R.M., Huson, D.H., Wortman, J. R., Zhang, Q., Kodira, C.D., Zheng, X.H., Chen, L., Skupski, M., Subramanian, G., Thomas, P.D., Zhang, J., Gabor Miklos, G.L., Nelson, C., Broder, S., Clark, A.G., Nadeau, J., McKusick, V.A., Zinder, N., Levine, A.J., Roberts, R.J., Simon, M., Slayman, C., Hunkapiller, M., Bolanos, R., Delcher, A., Dew, I., Fasulo, D., Flanigan, M., Florea, L., Halpern, A., Hannenhalli, S., Kravitz, S., Levy, S., Mobarry, C., Reinert, K., Remington, K., Abu-Threideh, J., Beasley, E., Biddick, K., Bonazzi, V., Brandon, R., Cargill, M., Chandramouliswaran, I., Charlab, R., Chaturvedi, K., Deng, Z., Di Francesco, V., Dunn, P., Eilbeck, K., Evangelista, C., Gabrielian, A.E., Gan, W., Ge, W., Gong, F., Gu, Z., Guan, P., Heiman, T.J., Higgins, M.E., Ji, R.R., Ke, Z., Ketchum, K. A., Lai, Z., Lei, Y., Li, Z., Li, J., Liang, Y., Lin, X., Lu, F., Merkulov, G.V., Milshina, N., Moore, H.M., Naik, A.K., Narayan, V.A., Neelam, B., Nusskern, D., Rusch, D.B., Salzberg, S., Shao, W., Shue, B., Sun, J., Wang, Z., Wang, A., Wang, X., Wang, J., Wei, M., Wides, R., Xiao, C., Yan, C. , Yao, A., Ye, J., Zhan, M., Zhang, W., Zhang, H., Zhao, Q., Zheng, L., Zhong, F., Zhong, W., Zhu, S., Zhao, S., Gilbert, D. , Baumhueter, S., Spier, G., Carter, C., Cravchik, A., Woodage, T., Ali, F., An, H., Awe, A., Baldwin, D., Baden, H., Barnstead, M., Barrow, I., Beeson, K., Busam, D., Carver, A., Center, A., Cheng, M.L., Curry, L., Danaher, S., Davenport, L. , Desilets, R., Dietz, S., Dodson, K., Doup, L., Ferriera, S., Garg, N., Gluecksmann, A., Hart, B., Haynes, J., Haynes, C., Heiner, C., Hladun, S., Hostin, D., Houck, J., Howland, T., Ibegwam, C., Johnson, J., Kalush, F., Kline, L., Koduru, S., Love, A., Mann, F., May, D., McCawley, S., McIntosh, T., McMullen, I., Moy, M., Moy, L., Murphy, B., Nelson, K., Pfannkoch, C., Pratts, E., Puri, V., Qureshi, H., Reardon, M., Rodriguez, R., Rogers, Y.H., Romblad, D., Ruhfel, B., Scott, R., Sitter, C., Smallwood, M., Stewart, E., Strong, R., Suh, E., Thomas, R., Tint, N.N., Tse, S., Vech, C., Wang, G., Wetter, J., Williams, S., Williams, M., Windsor, S., Winn-Deen, E., Wolfe, K., Zaveri, J., Zaveri, K., Abril, J.F., Guigo, R., Campbell, M.J., Sjolander, K.V., Karlak, B., Kejariwal, A., Mi, H., Lazareva, B., Hatton, T., Narechania, A., Diemer, K., Muruganujan, A., Guo, N., Sato, S., Bafna, V., Istrail, S., Lippert, R., Schwartz, R., Walenz, B., Yooseph, S., Allen, D., Basu, A., Baxendale, J., Blick, L., Caminha, M., Carnes-Stine, J., Caulk, P., Chiang, Y.H., Coyne, M., Dahlke, C., Mays, A., Dombroski, M., Donnelly, M., Ely, D., Esparham, S., Fosler, C., Gire, H., Glanowski, S., Glasser, K., Glodek, A., Gorokhov, M., Graham, K., Gropman, B., Harris, M., Heil, J., Henderson, S., Hoover, J., Jennings, D., Jordan, C., Jordan, J., Kasha, J., Kagan, L., Kraft, C., Levitsky, A., Lewis, M., Liu, X., Lopez, J., Ma, D., Majoros, W., McDaniel, J., Murphy, S., Newman, M., Nguyen, T., Nguyen, N., Nodell, M., Pan, S., Peck, J., Peterson, M., Rowe, W., Sanders, R., Scott, J., Simpson, M., Smith, T., Sprague, A., Stockwell, T., Turner, R., Venter, E., Wang, M., Wen, M., Wu, D., Wu, M., Xia, A., Zandieh, A., and Zhu, X., (2001) The sequence of the human genome. Science, 291 (5507), 1304-1351.
131. van Tellingen, O. (2001) The importance of drug-transporting P-glycoproteins in toxicology. Toxicology Letters, 120 (1-3), 31-41.
132. Lin, J.H. and Yamazaki, M. (2003) Clinical relevance of P-glycoprotein in drug therapy. Drug Metabolism Reviews, 35 (4), 417-454.
133. Kessel, D. and Bosmann, H.B. (1970) Effects of L-asparaginase on protein and glycoprotein synthesis. FEBS Letters, 10 (2), 85-88.
134. Juliano, R.L. and Ling, V. (1976) A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochimica et Biophysica Acta, 455 (1), 152-162.
135. Roninson, I.B., Abelson, H.T., Housman, D.E., Howell, N., and Varshavsky, A. (1984) Amplification of specific DNA sequences correlates with multi-drug resistance in Chinese hamster cells. Nature, 309, 626-628.
136. Shen, D.W., Fojo, A., Chin, J.E., Roninson, I.B., Richert, N., Pastan, I., and Gottesman, M.M. (1986) Human multidrug-resistant cell lines: increased mdr1 expression can precede gene amplification. Science, 232 (4750), 643-645.
137. Gros, P., Ben Neriah, Y.B., Croop, J.M., and Housman, D.E. (1986) Isolation and expression ofa complementary DNA that confers multidrug resistance. Nature, 323 (6090), 728-731.
138. Gros, P., Croop, J., Roninson, I., Varshavsky, A., and Housman, D.E. (1986) Isolation and characterization of DNA sequences amplified in multidrug-resistant hamster cells. Proceedings of the National Academy of Sciences ofthe United States of America, 83 (2), 337-341.
139. Gros, P., Raymond, M., Bell, J., and Housman, D. (1988) Cloning and characterization of a second member of the mouse mdr gene family. Molecular and Cellular Biology, 8 (7), 2770-2778.
140. Ueda, K., Clark, D.P., Chen, C.J., Roninson, I.B., Gottesman, M.M., and Pastan, I. (1987) The human multidrug resistance (mdr1) gene. cDNA cloning and transcription initiation. The Journal of Biological Chemistry, 262 (2), 505-508.
141. Shen, D.W., Fojo, A., Roninson, I.B., Chin, J.E., Soffir, R., Pastan, I., and Gottesman, M.M. (1986) Multidrug resistance of DNA-mediated transformants is linked to transfer of the human mdr1 gene. Molecular and Cellular Biology, 6 (11), 4039-4045.
142. Cai, J. and Gros, P. (2003) Overexpression, purification, and functional characterization of ATP-binding cassette transporters in the yeast, Pichia pastoris. Biochimica et Biophysica Acta, 1610 (1), 63-76.
143. Inaba, M. and Johnson, R.K. (1977) Decreased retention of actinomycin D as the basis for cross-resistance in anthracycline-resistant sublines of P388 leukemia. Cancer Research, 37 (12), 4629-4634.
144. Beck, W.T. (1987) The cell biology of multiple drug resistance. Biochemical Pharmacology, 36 (18), 2879-2887.
145. Beck, W.T. (1990) Multidrug resistance and its circumvention. European Journal of Cancer, 26 (4), 513-515.
146. Horio, M., Gottesman, M.M., and Pastan, I. (1988) ATP-dependent transport of vinblastine in vesicles from human multidrug-resistant cells. Proceedings ofthe National Academy of Sciences of the United States of America, 85 (10), 3580-3584.
147. Shapiro, A.B. and Ling, V. (1995) Reconstitution of drug transport by purified P-glycoprotein. The Journal of Biological Chemistry, 270 (27), 16167-16175.
148. Inaba, M., Kobayashi, H., Sakurai, Y., and Johnson, R.K. (1979) Active efflux of daunorubicin and adriamycin in sensitive and resistant sublines of P388 leukemia. Cancer Res, 39, 2200-2203.
149. Schinkel, A.H. and Borst, P. (1991) Multidrug resistance mediated by P-glycoproteins. Semin Cancer Biol, 2, 213-226.
150. van Zuylen, L., Verweij, J., Nooter, K., Brouwer, E., Stoter, G., and Sparreboom, A. (2000) Role ofintestinal P-glycoprotein in the plasma and fecal disposition of docetaxel in humans. Clinical Cancer Research, 6 (7), 2598-2603.
151. Efferth, T. and Osieka, R. (1993) Clinical relevance of the MDR1 gene and its gene product, P-glycoprotein, for cancer chemotherapy: a meta-analysis. Tumor Diagnostik und Therapie, 14, 238-243.
152. Jang, S.H., Wientjes, M.G., and Au, J.L. (2003) Interdependent effect of P-glycoprotein-mediated drug efflux and intracellular drug binding on intracellular paclitaxel pharmacokinetics: application of computational modelling. The Journal of Pharmacology and Experimental Therapeutics, 304 (2), 773-780.
153. Hendrikse, N.H., de Vries, E.G., Eriks-Fluks, L., van der Graaf, W.T., Hospers, G.A., Willemsen, A.T., Vaalburg, W., and Franssen, E.J. (1999) A new in vivo method to study P-glycoprotein transport in tumors and the blood-brain barrier. Cancer Research, 59 (10), 2411-2416.
154. Martin, C., Walker, J., Rothnie, A., and Callaghan, R. (2003) The expression of P-glycoprotein does influence the distribution of novel fluorescent compounds in solid tumour models. British Journal of Cancer, 89 (8), 1581-1589.
155. Cole, S.P., Bhardwaj, G., Gerlach, J.H., Mackie, J.E., Grant, C.E., Almquist, K.C., Stewart, A.J., Kurz, E.U., Duncan, A.M., and Deeley, R.G. (1992) Overexpressionof a transporter gene in a multidrug-resistant human lung cancer line. Science, 258, 1650-1654.
156. Jedlitschky, G., Leier, I., Buchholz, U., Center, M., and Keppler, D. (1996) Transport of glutathione glucuronate and sulfate conjugates by the MRP gene-encoded conjugate export pump. Cancer Research, 56, 988-994.
157. Jedlitschky, G., Leier, I., Buchholz, U., Center, M., and Keppler, D. (1994) ATP-dependent transport ofglutathione S-conjugates by multidrug resistance-associated protein. Cancer Research, 54, 4833-4836.
158. Westlake, C.J., Payen, L., Gao, M., Cole, S.P., and Deeley, R.G. (2004) Identification and characterization of functionally important elements in the multidrug resistance protein 1 COOH-terminal region. The Journal of Biological Chemistry, 279 (51), 53571-53583.
159. Bates, S.E. (2002) Solvingtheproblem of multidrug resistance: ABC transporters in clinical oncology, in ABC Proteins: From Bacteriato Man (eds K. Kuchler, S.P. Cole, and B. Holland), Academic Press, New York, pp. 65-80.
160. Wijnholds, J., de Lange, E.C.M., Scheffer, G.L., van der Berg, D.J., Mol, C.A.A.M., van der Valk, M., Schinkel, A.H., Scheper, R.J., Breimer, D.D., and Borst, P. (2000) Multidrug resistance protein 1 protects the choroid plexus epithelium and contributes to the blood-cerebrospinal fluid barrier. The Journal of Clinical Investigation, 105, 279-285.
161. Schinkel, A.H. (1997) The physiological function of drug-transporting P-glycoproteins. Seminars in Cancer Biology, 8 (3), 161-170.
162. Thiebaut, F., Tsuruo, T., Hamada, H., Gottesman, M.M., Pastan, I., and Willingham, M.C. (1987) Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proceedings ofthe National Academy of Sciences of the United States of America, 84 (21), 7735-7738.
163. Cordon-Cardo, C., O'Brien, J.P., Boccia, J., Casals, D., Bertino, J.R., and Melamed, M.R. (1990) Expression of the multidrug resistance gene product (P-glycoprotein) in human normal and tumor tissues. The Journal of Histochemistry and Cytochemistry, 38 (9), 1277-1287.
164. Regina, A., Koman, A., Piciotti, M., El Hafny, B., Center, M.S., Bergmann, R., Couraud, P.O., and Roux, F. (1998) Mrp1 multidrug resistance-associated protein and P-glycoprotein expression in rat brain microvessel endothelial cells. Journal of Neurochemistry, 71 (2), 705-715.
165. Sugawara, I., Koji, T., Ueda, K., Pastan, I., Gottesman, M.M., Nakane, P.K., and Mori, S. (1990) In situ localization of the human multidrug-resistance gene mRNA using thymine-thymine dimerized singlestranded cDNA. Jpn J Cancer Res, 81, 949-955.
166. Sugawara, I., Kataoka, I., Morishita, Y., Hamada, H., Tsuruo, T., Itoyama, S., and Mori, S. (1988) Tissue distribution of P-glycoprotein encoded by a multidrug-resistant gene as revealedby a monoclonal antibody, MRK16. Cancer Research, 48 (7), 1926-1929.
167. Croop, J.M., Raymond, M., Haber, D., Devault, A., Arceci, R.J., Gros, P., and Housman, D.E. (1989) The three mouse multidrug resistance (mdr) genes are expressed in a tissue-specific manner in normal mouse tissues. Molecular and Cellular Biology, 9 (3), 1346-1350.
168. Borst, P. and Elferink, R.O. (2002) Mammalian ABC transporters in health and disease. Annual Review of Biochemistry, 71, 537-592.
169. Chaudhary, P.M. and Roninson, I.B. (1991) Expression and activity of P-glycoprotein, a multidrug efflux pump, in human hematopoietic stem cells. Cell, 66 (1), 85-94.
170. Wang, G., Pincheira, R., Zhang, M., and Zhang, J.T. (1997) Conformational changes of P-glycoprotein by nucleotide binding. The Biochemical Journal, 328 (Pt 3), 897-904.
171. Julien, M. and Gros, P. (2000) Nucleotide-induced conformational changes in P-glycoprotein and in nucleotide binding site mutants monitored by trypsin sensitivity. Biochemistry, 39 (15), 4559-4568.
172. Sonveaux, N., Vigano, C., Shapiro, A.B., Ling, V., and Ruysschaert, J.M. (1999) Ligand-mediated tertiary structure changes of reconstituted P-glycoprotein. A tryptophan fluorescence quenching analysis. The Journal of Biological Chemistry, 274 (25), 17649-17654.
173. Liu, R., Siemiarczuk, A., and Sharom, F.J. (2000) Intrinsic fluorescence of the P-glycoprotein multidrug transporter: sensitivity of tryptophan residues to binding of drugs and nucleotides. Biochemistry, 39 (48), 14927-14938.
174. Sonveaux, N., Shapiro, A.B., Goormaghtigh, E., Ling, V., and Ruysschaert, J.M. (1996) Secondary and tertiary structure changes ofreconstituted P-glycoprotein. A Fourier transform attenuated total reflection infrared spectroscopy analysis. The Journal of Biological Chemistry, 271 (40), 24617-24624.
175. Druley, T.E., Stein, W.D., and Roninson, I.B. (2001) Analysis of MDR1 P-glycoprotein conformational changes in permeabilized cells using differential immunoreactivity. Biochemistry, 40 (14), 4312-4322.
176. Druley, T.E., Stein, W.D., Ruth, A., and Roninson, I.B. (2001) P-glycoprotein-mediated colchicine resistance in different cell lines correlates with the effects of colchicine on P-glycoprotein conformation. Biochemistry, 40 (14), 4323-4331.
177. Ruth, A., Stein, W.D., Rose, E., and Roninson, I.B. (2001) Coordinatechanges in drug resistance and drug-induced conformational transitions in altered-function mutants of the multidrug transporter P-glycoprotein. Biochemistry, 40 (14), 4332-4339.
178. Dawson, R.J. and Locher, K.P. (2007) Structure of the multidrug ABC transporter Sav1866 from Staphylococcus aureus in complex with AMP-PNP. FEBS Letters, 581, 935-938.
179. Higgins, C.F. and Gottesman, M.M. (1992) Is the multidrug transporter a flippase? Trends in Biochemical Sciences, 17 (1), 18-21.
180. Homolya, L., Hollo, Z., Germann, U.A., Pastan, I., Gottesman, M.M., and Sarkadi, B. (1993) Fluorescent cellular indicators are extruded by the multidrug resistance protein. The Journal of Biological Chemistry, 268 (29), 21493-21496.
181. Raviv, Y., Pollard, H.B., Bruggemann, E.P., Pastan, I., and Gottesman, M.M. (1990) Photosensitized labeling of a functional multidrug transporter in living drug-resistant tumor cells. The Journal of Biological Chemistry, 265 (7), 3975-3980.
182. Eytan, G.D., Regev, R., Oren, G., and Assaraf, Y.G. (1996) The role of passive transbilayer drug movement in multidrug resistance and its modulation. The Journal of Biological Chemistry, 271 (22), 12897-12902.
183. Eytan, G.D., Regev, R., Oren, G., Hurwitz, C.D., and Assaraf, Y.G. (1997) Efficiency of P-glycoprotein-mediated exclusion of rhodamine dyes from multidrug-resistant cells is determined by their passive transmembrane movement rate. European Journal of Biochemistry, 248 (1), 104-112.
184. Choi, K., Chen, C.-J., Kriegler, M., and Roninson, I.B. (1988) An altered pattern ofcross-resistance in multidrug resistant human cells results from spontaneous mutations in the mdr1 (P-glycoprotein) gene. Cell, 53, 519-529.
185. Dhir, R., Grizzuti, K., Kajiji, S., and Gros, P. (1993) Modulatory effects on substrate specificity of independent mutations at the serine 939/941 position in predicted transmembrane domain 11 of P-glycoprotein. Biochemistry, 32, 9492-9499.
186. Zhang, X., Collins, K.I., and Greenberger, L.M. (1995) Functional evidence that transmembrane 12 and the loop between transmembrane 11 and 12 form part of the drug-binding domain in P-glycoprotein encoded by MDR1. The Journal of Biological Chemistry, 270 (10), 5441-5448.
187. Bruggemann, E.P., Currier, S.J., Gottesman, M.M., and Pastan, I. (1992) Characterization of the azidopine and vinblastine binding site of P-glycoprotein. The Journal of Biological Chemistry, 267 (29), 21020-21026.
188. Demeule, M., Jodoin, J., Gingras, D., and Beliveau, R. (2000) P-glycoprotein is localized in caveolae in resistant cells and in brain capillaries. FEBS Letters, 466 (2-3), 219-224.
189. Demmer, A., Thole, H., Kubesch, P., Brandt, T., Raida, M., Fislage, R., and Tummler, B. (1997) Localization of the iodomycin binding site in hamster P-glycoprotein. The Journal of Biological Chemistry, 272 (33), 20913-20919.
190. Greenberger, L.M. (1993) Major photoaffinity labeling sites for iodoaryl azidoprazosin in P-glycoprotein are within or immediately C-terminal to transmembrane domains 6 and 12. The Journal of Biological Chemistry, 268, 11417-11425.
191. 2+ channel by photoaffinity labelling. Trends in Pharmacological Sciences, 8, 95-100.
192. Tamai, I., and Safa, A.R. (1991) Azidopine noncompetitively interacts with vinblastine and cyclosporin A binding to P-glycoprotein in multidrug resistant cells. J Biol Chem, 266, 16796-16800.
193. Martin, C., Berridge, G., Higgins, C.F., and Callaghan, R. (1997) The multi-drug resistance reversal agent SR33557 and modulation of vinca alkaloid binding to P-glycoprotein by an allosteric interaction. British Journal of Pharmacology, 122, 765-771.
194. Ferry, D.R., Russell, M.A., and Cullen, M.H. (1992) P-glycoprotein possesses a 1,4-dihydropyridine-selective drug acceptor site which is alloserically coupled to a vinca-alkaloid-selective binding site. Biochem Biophys Res Commun, 188, 440-445.
195. Malkhandi, J., Ferry, D.R., Boer, R., Gekeler, V., Ise, W., and Kerr, D.J. (1994) Dexniguldipine-HCl is a potent allosteric inhibitor of [3H]vinblastine binding to P-glycoprotein of CCRF ADR 5000 cells. Eur J Pharmacol, 288, 105-114.
196. Loo, T.W., Bartlett, M.C., and Clarke, D.M. (2006) Transmembrane segment 1 of human P-glycoprotein contributes to the drug-binding pocket. The Biochemical Journal, 396, 537-545.
197. Loo, T.W. and Clarke, D.M. (2000) Identification of residues within the drugbinding domain of the human multidrug resistance P-glycoprotein by cysteinescanning mutagenesis and reaction with dibromobimane. The Journal of Biological Chemistry, 275, 39272-39278.
198. Pleban, K., Kopp, S., Csaszar, E., Peer, M., Hrebicek, T., Rizzi, A., Ecker, G.F., and Chiba, P. (2005) P-glycoprotein substrate binding domains are located at the transmembrane domain/transmembrane domain interfaces: a combined photoaffinity labeling-protein homology modeling approach. Molecular Pharmacology, 67, 365-374.
199. Loo, T.W., Bartlett, M.C., and Clarke, D.M. (2003) Permanent activation of the human P-glycoprotein by covalent modification of a residue in the drugbinding site. The Journal of Biological Chemistry, 278, 20449-20452.
200. Loo, T.W., Bartlett, M.C., and Clarke, D.M. (2004) The drug-binding pocket of the human multidrug resistance P-glycoprotein is accessible to the aqueous medium. Biochemistry, 43, 12081-12089.
201. Loo, T.W. and Clarke, D.M. (1997) Identification of residues in the drugbinding site of human P-glycoprotein usingathiol-reactive substrate. The Journal of Biological Chemistry, 272, 31945-31948.
202. Rothnie, A., Storm, J., Campbell, J., Linton, K.J., Kerr, I.D., and Callaghan, R. (2004) The topography oftransmembrane segment six is altered during the catalytic cycle of P-glycoprotein. The Journal of Biological Chemistry, 279, 34913-34921.
203. Loo, T.W., Bartlett, M.C., and Clarke, D.M. (2006) Transmembrane segment 7 of human P-glycoprotein forms part of the drug-binding pocket. The Biochemical Journal, 399, 351-359.
204. Loo, T.W. and Clarke, D.M. (1999) Identification of residues in the drug-binding domain of human P-glycoprotein. Analysis of transmembrane segment 11 by cysteinescanning mutagenesis and inhibition by dibromobimane. The Journal of Biological Chemistry, 274, 35388-35392.
205. Safa, A.R. (1993) Photoaffinity labeling of P-glycoprotein in multidrug-resistant cells. Cancer Investigation, 11, 46-56.
206. Taguchi, Y., Kino, K., Morishima, M., Komano, T., Kane, S.E., and Ueda, K. (1997) Alteration of substrate specificity by mutations at the His61 position in predicted transmembrane domain 1 of human MDR1/P-glycoprotein. Biochemistry, 36, 8883-8889.
207. Taguchi, Y., Morishima, M., Komano, T., and Ueda, K. (1997) Amino acid substitutions in the first transmembrane domain (TM1) of P-glycoprotein that alter substrate specificity. FEBS Letters, 413, 142-146.
208. Ma, J.F., Grant, G., and Melera, P.W. (1997) Mutations in the sixth transmembrane domain of P-glycoprotein that alter the pattern of cross-resistance also alter sensitivity to cyclosporin A reversal. Molecular Pharmacology, 51, 922-930.
209. 125I] iodoarylazidoprazosin labelling. Molecular Pharmacology, 60, 254-261.
210. Hanna, M., Brault, M., Kwan, T., Kast, C., and Gros, P. (1996) Mutagenesis of transmembrane domain 11 of P-glycoprotein by alanine scanning. Biochemistry, 35, 3625-3635.
211. Hafkemeyer, P., Dey, S., Ambudkar, S.V., Hrycyna, C.A., Pastan, I., and Gottesman, M.M. (1998) Contribution to substrate specificity and transport ofnonconserved residues in transmembrane domain12 of human P-glycoprotein. Biochemistry, 37, 16400-16409.
212. Demeule, M., Laplante, A., Murphy, G.F., Wenger, R.M., and Beliveau, R. (1998) Identification of the cyclosporin-binding site in P-glycoprotein. Biochemistry, 37, 18110-18118.
213. Loo, T.W. and Clarke, D.M. (1995) Identification of residues in the drugbinding site of human P-glycoprotein. Journal of Biological Chemistry, 272, 31945-31948.
214. Taylor, A.M., Storm, J., Soceneantu, L., Linton, K.J., Gabriel, M., Martin, C., Woodhouse, J., Blott, E.J., Higgins, C.F., and Callaghan, R. (2001) Detailed characterization of cysteine-less P-glycoprotein reveals subtle pharmacological differences in function from wild-type protein. British Journal of Pharmacology, 134, 1609-1618.
215. Rothnie, A., Storm, J., McMahon, R., Taylor, A., Kerr, I.D., and Callaghan, R. (2005) The coupling mechanism of P-glycoprotein involves residue L339 in the sixth membrane spanning segment. FEBS Letters, 579, 3984-3990.
216. Brockman, R.W. (1963) Mechanisms of resistance to anticancer agents. Advances in Cancer Research, 57, 129-234.
217. Hutchison, D.J. (1963) Cross resistance and collateral sensitivity studies in cancer chemotherapy. Advances in Cancer Research, 57, 235-250.
218. Didziapetris, R., Japertas, P., Avdeef, A., and Petrauskas, A. (2003) Classification analysis of P-glycoprotein substrate specificity. Journal of Drug Targeting, 11, 391.
219. Agrawal, M., Abraham, J., Balis, F.M., Edgerly, M., Stein, W.D., Bates, S., Fojo, T., and Chen, C.C. (2003) Increased 99mTc-sestamibi accumulation in normal liver and drug-resistant tumors after the administration of the glycoprotein inhibitor, XR9576. Clinical Cancer Research, 9 (2), 650-656.
220. Ganapathi, R. and Grabowski, D. (1983) Enhancement of sensitivity to adriamycin in resistant P388 leukemia by the calmodulin inhibitor trifluoperazine. Cancer Research, 43 (8), 3696-3699.
221. Goldberg, H., Ling, V., Wong, P.Y., and Skorecki, K. (1988) Reduced cyclosporin accumulation in multidrug-resistant cells. Biochemical and Biophysical Research Communications, 152 (2), 552-558.
222. Ramu, A., Fuks, Z., Gatt, S., and Glaubiger, D. (1984) Reversal ofacquired resistance to doxorubicin in P388 murine leukemia cells by perhexiline maleate. Cancer Research, 44 (1), 144-148.
223. Tsuruo, T., Iida, H., Kitatani, Y., Yokota, K., Tsukagoshi, S., and Sakurai, Y. (1984) Effects of quinidine and related compounds on cytotoxicity and cellular accumulation of vincristine and adriamycin in drug-resistant tumor cells. Cancer Research, 44 (10), 4303-4307.
224. Tsuruo, T., Iida, H., Tsukagoshi, S., and Sakurai, J. (1981) Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Research, 41, 1967-1972.
225. Benson, A.B., 3rd, Trump, D.L., Koeller, J.M., Egorin, M.I., Olman, E.A., Witte, R.S., Davis, T.E., and Tormey, D.C. (1985) Phase I studyofvinblastine andverapamil given by concurrent iv infusion. Cancer Treatment Reports, 69 (7-8), 795-799.
226. Cairo, M.S., Siegel, S., Anas, N., and Sender, L. (1989) Clinical trial of continuous infusion verapamil, bolus vinblastine, and continuous infusion VP-16 in drug-resistant pediatric tumors. Cancer Research, 49 (4), 1063-1066.
227. Bartlett, N.L., Lum, B.L., Fisher, G.A., Brophy, N.A., Ehsan, M.N., Halsey, J., and Sikic, B.I. (1994) Phase I trial of doxorubicin with cyclosporine as a modulator of multidrug resistance. Journal of Clinical Oncology, 12 (4), 835-842.
228. Verweij, J., Herweijer, H., Oosterom, R., van der Burg, M.E., Planting, A.S., Seynaeve, C., Stoter, G., and Nooter, K. (1991) Aphase II study of epidoxorubicin in colorectal cancer and the use of cyclosporin-A in an attempt to reverse multidrug resistance. British Journal of Cancer, 64 (2), 361-364.
229. Plumb, J.A., Milroy, R., and Kaye, S.B. (1990) The activity of verapamil as a resistance modifier in vitro in drug resistant human tumour cell lines is not stereospecific. Biochemical Pharmacology, 39 (4), 787-792.
230. Bissett, D., Kerr, D.J., Cassidy, J., Meredith, P., Traugott, U., and Kaye, S.B. (1991) Phase I and pharmacokinetic study of D-verapamil and doxorubicin. British Journal of Cancer, 64 (6), 1168-1171.
231. Kornek, G., Raderer, M., Schenk, T., Pidlich, J., Schulz, F., Globits, S., Tetzner, C., and Scheithauer, W. (1995) Phase I/II trial of dexverapamil, epirubicin, and granulocyte-macrophage-colony stimulating factor in patients with advanced pancreatic adenocarcinoma. Cancer, 76 (8), 1356-1362.
232. Twentyman, P.R. and Bleehen, N.M. (1991) Resistance modification by PSC-833, a novel non-immunosuppressive cyclosporin [corrected]. European Journal of Cancer, 27 (12), 1639-1642.
233. Giaccone, G., Linn, S.C., Welink, J., Catimel, G., Stieltjes, H., van der Vijgh, W.J., Eeltink, C., Vermorken, J.B., and Pinedo, H.M. (1997) A dose-finding and pharmacokinetic study of reversal of multidrug resistance with SDZ PSC 833 in combination with doxorubicin in patients with solid tumors. Clinical Cancer Research, 3 (11), 2005-2015.
234. Boote, D.J., Dennis, I.F., Twentyman, P.R., Osborne, R.J., Laburte, C., Hensel, S., Smyth, J.F., Brampton, M.H., and Bleehen, N.M. (1996) Phase I study of etoposide with SDZ PSC 833 as a modulator of multidrug resistance in patients with cancer. Journal of Clinical Oncology, 14 (2), 610-618.
235. Friedenberg, W.R., Rue, M., Blood, E.A., Dalton, W.S., Shustik, C., Larson, R.A., Sonneveld, P., and Greipp, P.R. (2006) Phase III study of PSC-833 (valspodar) in combination with vincristine, doxorubicin, and dexamethasone (valspodar/VAD) versus VAD alone in patients with recurring or refractory multiple myeloma (E1A95): a trial of the Eastern Cooperative Oncology Group. Cancer, 106 (4), 830-838.
236. Hyafil, F., Vergely, C., Du Vignaud, P., and Grand-Perret, T. (1993) In vitro and in vivo reversal of multidrug resistance by GF120918, an acridonecarboxamide derivative. Cancer Research, 53 (19), 4595-4602.
237. Roe, M., Folkes, A., Ashworth, P., Brumwell, J., Chima, L., Hunjan, S., Pretswell, I., Dangerfield, W., Ryder, H., and Charlton, P. (1999) Reversal of P-glycoprotein mediated multidrug resistance by novel anthranilamide derivatives. Bioorganic & Medicinal Chemistry Letters, 9 (4), 595-600.
238. Pusztai, L., Wagner, P., Ibrahim, N., Rivera, E., Theriault, R., Booser, D., Symmans, F.W., Wong, F., Blumenschein, G., Fleming, D.R., Rouzier, R., Boniface, G., and Hortobagyi, G.N. (2005) Phase II study of tariquidar, a selective P-glycoprotein inhibitor, in patients with chemotherapy-resistant, advanced breast carcinoma. Cancer, 104 (4), 682-691.
239. Pearce, H.L., Safa, A.R., Bach, N.J., Winter, M.A., Cirtain, M.C., and Beck, W.T. (1989) Essential features of the P-glycoprotein pharmacophore as defined by a series of reserpine analogs that modulate multidrug resistance. Proceedings of the National Academy of Sciences of the United States of America, 86 (13), 5128-5132.
240. Zamora, J.M., Pearce, H.L., and Beck, W.T. (1988) Physical-chemical properties shared by compounds that modulate multidrug resistance in human leukemic cells. Molecular Pharmacology, 33 (4), 454-462.
241. Scala, S., Akhmed, N., Rao, U.S., Paull, K., Lan, L.B., Dickstein, B., Lee, J.S., Elgemeie, G.H., Stein, W.D., and Bates, S.E. (1997) P-glycoprotein substrates and antagonists cluster into two distinct groups. Molecular Pharmacology, 51 (6), 1024-1033.
242. Seelig, A. (1998) A general pattern for substrate recognition by P-glycoprotein. European Journal of Biochemistry, 251 (1-2), 252-261.
243. Seelig, A. and Landwojtowicz, E. (2000) Structure-activity relationship of P-glycoprotein substrates and modifiers. European Journal of Pharmaceutical Sciences, 12, 31-40.
244. Raad, I., Terreux, R., Richomme, P., Matera, E.L., Dumontet, C., Raynaud, J., and Guilet, D. (2006) Structure-activity relationship of natural and synthetic coumarins inhibiting the multidrug transporter P-glycoprotein. Bioorganic and Medicinal Chemistry, 14 (20), 6979-6987.
245. Kaiser, D., Smiesko, M., Kopp, S., Chiba, P., and Ecker, G.F. (2005) Interaction field based and hologram based QSAR analysis of propafenone-type modulators of multidrug resistance. Medicinal Chemistry, 1 (5), 431-444.
246. Labrie, P., Maddaford, S.P., Fortin, S., Rakhit, S., Kotra, L.P., and Gaudreault, R.C. (2006) A comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) of anthranilamide derivatives that are multidrug resistance modulators. Journal of Medicinal Chemistry, 49 (26), 7646-7660.
247. Cianchetta, G., Singleton, R.W., Zhang, M., Wildgoose, M., Giesing, D., Fravolini, A., Cruciani, G., and Vaz, R.J. (2005) A pharmacophore hypothesis for P-glycoprotein substrate recognition using GRIND-based 3D-QSAR. Journal of Medicinal Chemistry, 48 (8), 2927-2935.
248. Aller, S.G., Yu, J., Ward, A., Weng, Y., Chittaboina, S., Zhuo, R., Harrell, P.M., Trinh, Y.T., Zhang, Q., Urbatsch, I.L., and Chang, G. (2009) Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science, 323, 1718-1722.
249. Kadaba, N.S., Kaiser, J.T., Johnson, E., Lee, A., and Rees, D.C. (2008) The high-affinity E. coli methionine ABC transporter: structure and allosteric regulation. Science, 321, 250-253.
250. Khare, D., Oldham, M.L., Orelle, C., Davidson, A.L., and Chen, J. (2009) Alternating access in maltose transporter mediated by rigid-body rotations. Mol Cell, 33, 528-536.