SpringerProtocols: Abstract: Molecular Mechanism of ATP-Dependent Solute Transport by Multidrug Resistance-Associated Protein 1

11. Molecular Mechanism of ATP-Dependent Solute Transport by Multidrug Resistance-Associated Protein 1

By: Xiu-bao Chang¹

Abstract

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Millions of new cancer patients are diagnosed each year and over half of these patients die from this devastating disease. Thus, cancer causes a major public health problem worldwide. Chemotherapy remains the principal mode to treat many metastatic cancers. However, occurrence of cellular multidrug resistance (MDR) prevents efficient killing of cancer cells, leading to chemotherapeutic treatment failure. Over-expression of ATP-binding cassette transporters, such as P-glycoprotein, breast cancer resistance protein and/or multidrug resistance-associated protein 1 (MRP1), confers an acquired MDR due to their capabilities of transporting a broad range of chemically diverse anticancer drugs across the cell membrane barrier. In this review, the molecular mechanism of ATP-dependent solute transport by MRP1 will be addressed.

Affiliation(s): (1) Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA

Book Title: Multi-Drug Resistance in Cancer

Series: Methods in Molecular Biology | Volume: 596 | Pub. Date: Oct-23-2009 | Page Range: 223-249 | DOI: 10.1007/978-1-60761-416-6_11

Subject: Cancer Research

Key Words: MRP1 - ATP - NBD - GSH - Transport - MDR

References

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1.	Choudhuri S, Klaassen CD (2006) Structure, function, expression, genomic organization, and single nucleotide polymorphisms of human ABCB1 (MDR1), ABCC (MRP), and ABCG2 (BCRP) efflux transporters. Int J Toxicol 25:231–259

2.	Cole SP, Bhardwaj G, Gerlach JH et al (1992) Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line (see comments). Science 258:1650–1654

3.	Mirski SE, Gerlach JH, Cole SP (1987) Multidrug resistance in a human small cell lung cancer cell line selected in adriamycin. Cancer Res 47:2594–2598

4.	Slovak ML, Ho JP, Bhardwaj G et al (1993) Localization of a novel multidrug resistance-associated gene in the HT1080/DR4 and H69AR human tumor cell lines. Cancer Res 53:3221–3225

5.	Grant CE, Kurz EU, Cole SP, Deeley RG (1997) Analysis of the intron-exon organization of the human multidrug-resistance protein gene (MRP) and alternative splicing of its mRNA. Genomics 45:368–378

6.	Grant CE, Valdimarsson G, Hipfner DR et al (1994) Overexpression of multidrug resistance-associated protein (MRP) increases resistance to natural product drugs. Cancer Res 54:357–361

7.	Marquardt D, McCrone S, Center MS (1990) Mechanisms of multidrug resistance in HL60 cells: detection of resistance-associated proteins with antibodies against synthetic peptides that correspond to the deduced sequence of P-glycoprotein. Cancer Res 50:1426–1430

8.	Krishnamachary N, Center MS (1993) The MRP gene associated with a non-P-glycoprotein multidrug resistance encodes a 190-kDa membrane bound glycoprotein. Cancer Res 53:3658–3661

9.	Juliano RL, Ling V (1976) A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta 455:152–162

10.	Chen CJ, Chin JE, Ueda K et al (1986) Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell 47:381–389

11.	Hipfner DR, Deeley RG, Cole SP (1999) Structural, mechanistic and clinical aspects of MRP1. Biochim Biophys Acta 1461:359–376

12.	Borst P, Evers R, Kool M, Wijnholds J (1999) The multidrug resistance protein family. Biochim Biophys Acta 1461:347–357

13.	Dean M, Rzhetsky A, Allikmets R (2001) The human ATP-binding cassette (ABC) transporter superfamily. Genome Res 11:1156–1166

14.	Cole SP, Deeley RG (1998) Multidrug resistance mediated by the ATP-binding cassette transporter protein MRP. Bioessays 20:931–940

15.	Gao M, Cui HR, Loe DW et al (2000) Comparison of the functional characteristics of the nucleotide binding domains of multidrug resistance protein 1. J Biol Chem 275:13098–13108

16.	Zhang JT, Ling V (1991) Study of membrane orientation and glycosylated extracellular loops of mouse P-glycoprotein by in vitro translation. J Biol Chem 266:18224–18232

17.	Gros P, Croop J, Housman D (1986) Mammalian multidrug resistance gene: complete cDNA sequence indicates strong homology to bacterial transport proteins. Cell 47:371–380

18.	Gerlach JH, Endicott JA, Juranka PF et al (1986) Homology between P-glycoprotein and a bacterial haemolysin transport protein suggests a model for multidrug resistance. Nature 324:485–489

19.	Bakos E, Hegedus T, Hollo Z et al (1996) Membrane topology and glycosylation of the human multidrug resistance-associated protein. J Biol Chem 271:12322–12326

20.	Hipfner DR, Almquist KC, Leslie EM et al (1997) Membrane topology of the multidrug resistance protein (MRP). A study of glycosylation-site mutants reveals an extracytosolic NH2 terminus. J Biol Chem 272:23623–23630

21.	Borst P, Evers R, Kool M, Wijnholds J (2000) A family of drug transporters: the multidrug resistance-associated proteins. J Natl Cancer Inst 92:1295–1302

22.	Riordan JR, Rommens JM, Kerem B et al (1989) Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245:1066–1073

23.	Lee SH, Altenberg GA (2003) Transport of leukotriene C4 by a cysteine-less multidrug resistance protein 1 (MRP1). Biochem J 370:357–360

24.	Bakos E, Evers R, Szakacs G et al (1998) Functional multidrug resistance protein (MRP1) lacking the N-terminal transmembrane domain. J Biol Chem 273:2167–32175

25.	Krishnamachary N, Ma L, Zheng L, Safa AR, Center MS (1994) Analysis of MRP gene expression and function in HL60 cells isolated for resistance to adriamycin. Oncol Res 6:119–127

26.	Almquist KC, Loe DW, Hipfner DR et al (1995) Characterization of the M(r) 190, 000 multidrug resistance protein (MRP) in drug-selected and transfected human tumor cell. Cancer Res 55:102–110

27.	Flens MJ, Zaman GJ, van der Valk P et al (1996) Tissue distribution of the multidrug resistance protein. Am J Pathol 148:1237–1247

28.	St-Pierre MV, Serrano MA, Macias RI et al (2000) Expression of members of the multidrug resistance protein family in human term placenta. Am J Physiol Regul Integr Comp Physiol 279:R1495–R1503

29.	Zaman GJ, Versantvoort CH, Smit JJ et al (1993) Analysis of the expression of MRP, the gene for a new putative transmembrane drug transporter, in human multidrug resistant lung cancer cell lines. Cancer Res 53:1747–1750

30.	Nishino J, Suzuki H, Sugiyama D et al (1999) Transepithelial transport of organic anions across the choroid plexus: possible involvement of organic anion transporter and multidrug resistance-associated protein. J Pharmacol Exp Ther 290:289–294

31.	Choudhuri S, Cherrington NJ, Li N, Klaassen CD (2003) Constitutive expression of various xenobiotic and endobiotic transporter mRNAs in the choroid plexus of rats. Drug Metab Dispos 31:1337–1345

32.	Atkinson DE, Greenwood SL, Sibley CP, Glazier JD, Fairbairn LJ (2003) Role of MDR1 and MRP1 in trophoblast cells, elucidated using retroviral gene transfer. Am J Physiol Cell Physiol 285:C584–C591

33.	Brechot JM, Hurbain I, Fajac A, Daty N, Bernaudin JF (1998) Different pattern of MRP localization in ciliated and basal cells from human bronchial epithelium. J Histochem Cytochem 46:513–517

34.	Lohoff M, Prechtl S, Sommer F et al (1998) A multidrug-resistance protein (MRP)-like transmembrane pump is highly expressed by resting murine T helper (Th) 2, but not Th1 cells, and is induced to equal expression levels in Th1 and Th2 cells after antigenic stimulation in vivo. J Clin Invest 101:703–710

35.	Leslie EM, Deeley RG, Cole SP (2005) Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense. Toxicol Appl Pharmacol 204:216–237

36.	Nagashige M, Ushigome F, Koyabu N et al (2003) Basal membrane localization of MRP1 in human placental trophoblast. Placenta 24:951–958

37.	Pascolo L, Fernetti C, Pirulli D et al (2003) Effects of maturation on RNA transcription and protein expression of four MRP genes in human placenta and in BeWo cells. Biochem Biophys Res Commun 303:259–265

38.	Peng KC, Cluzeaud F, Bens M et al (1999) Tissue and cell distribution of the multidrug resistance-associated protein (MRP) in mouse intestine and kidney. J Histochem Cytochem 47:757–768

39.	St-Pierre MV, Stallmach T, Freimoser Grundschober A et al (2004) Temporal expression profiles of organic anion transport proteins in placenta and fetal liver of the rat. Am J Physiol Regul Integr Comp Physiol 287:R1505–R1516

40.	Stride BD, Valdimarsson G, Gerlach JH et al (1996) Structure and expression of the messenger RNA encoding the murine multidrug resistance protein, an ATP-binding cassette transporter. Mol Pharmacol 49:962–971

41.	Tribull TE, Bruner RH, Bain LJ (2003) The multidrug resistance-associated protein 1 transports methoxychlor and protects the seminiferous epithelium from injury. Toxicol Lett 142:61–70

42.	Wijnholds J, Scheffer GL, van der Valk M et al (1998) Multidrug resistance protein 1 protects the oropharyngeal mucosal layer and the testicular tubules against drug-induced damage. J Exp Med 188:797–808

43.	Wright SR, Boag AH, Valdimarsson G et al (1998) Immunohistochemical detection of multidrug resistance protein in human lung cancer and normal lung. Clin Cancer Res 4:2279–2289

44.	Deeley RG, Westlake C, Cole SP (2006) Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins. Physiol Rev 86:849–899

45.	Wijnholds J, deLange EC, Scheffer GL et al (2000) Multidrug resistance protein 1 protects the choroid plexus epithelium and contributes to the blood-cerebrospinal fluid barrier. J Clin Invest 105:279–285

46.	Mercier C, Masseguin C, Roux F, Gabrion J, Scherrmann JM (2004) Expression of P-glycoprotein (ABCB1) and Mrp1 (ABCC1) in adult rat brain: focus on astrocytes. Brain Res 1021:32–40

47.	de Lange EC (2004) Potential role of ABC transporters as a detoxification system at the blood-CSF barrier. Adv Drug Deliv Rev 56:1793–1809

48.	Bart J, Hollema H, Groen HJ et al (2004) The distribution of drug-efflux pumps, Pgp, BCRP, MRP1 and MRP2, in the normal blood-testis barrier and in primary testicular tumours. Eur J Cancer 40:2064–2070

49.	Cha SH, Sekine T, Fukushima JI et al (2001) Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol 59:1277–1286

50.	Schaub TP, Kartenbeck J, Konig J et al (1999) Expression of the MRP2 gene-encoded conjugate export pump in human kidney proximal tubules and in renal cell carcinoma. J Am Soc Nephrol 10:1159–69

51.	Evers R, Zaman GJ, van Deemter L et al (1996) Basolateral localization and export activity of the human multidrug resistance-associated protein in polarized pig kidney cells. J Clin Invest 97:1211–1218

52.	Westlake CJ, Qian YM, Gao M et al (2003) Identification of the structural and functional boundaries of the multidrug resistance protein 1 cytoplasmic loop 3. Biochemistry 42:14099–14113

53.	Hipfner DR, Gauldie SD, Deeley RG, Cole SP (1994) Detection of the M(r) 190, 000 multidrug resistance protein, MRP, with monoclonal antibodies. Cancer Res 54:5788–5792

54.	Roelofsen H, Vos TA, Schippers IJ et al (1997) Increased levels of the multidrug resistance protein in lateral membranes of proliferating hepatocyte-derived cells. Gastroenterology 112:511–521

55.	Thiebaut F, Tsuruo T, Hamada H et al (1987) Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc Natl Acad Sci USA 84:7735–7738

56.	Kartenbeck J, Leuschner U, Mayer R, Keppler D (1996) Absence of the canalicular isoform of the MRP gene-encoded conjugate export pump from the hepatocytes in Dubin–Johnson syndrome. Hepatology 23:1061–1066

57.	Maliepaard M, Scheffer GL, Faneyte IF et al (2001) Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues. Cancer Res 61:3458–3464

58.	Hoogeveen AT, Keulemans J, Willemsen R et al (1991) Immunological localization of cystic fibrosis candidate gene products. Exp Cell Res 193:435–437

59.	Marino CR, Matovcik LM, Gorelick FS, Cohn JA (1991) Localization of the cystic fibrosis transmembrane conductance regulator in pancreas. J Clin Invest 88:712–716

60.	Crawford I, Maloney PC, Zeitlin PL et al (1991) Immunocytochemical localization of the cystic fibrosis gene product CFTR. Proc Natl Acad Sci USA 88:9262–9266

61.	Jedlitschky G, Leier I, Buchholz U et al (1996) Transport of glutathione, glucuronate, and sulfate conjugates by the MRP gene-encoded conjugate export pump. Cancer Res 56:988–994

62.	Loe DW, Almquist KC, Deeley RG, Cole SP (1996) Multidrug resistance protein (MRP)-mediated transport of leukotriene C4 and chemotherapeutic agents in membrane vesicles. Demonstration of glutathione-dependent vincristine transport. J Biol Chem 271:9675–9682

63.	Renes J, de Vries EG, Nienhuis EF, Jansen PL, Muller M (1999) ATP- and glutathione-dependent transport of chemotherapeutic drugs by the multidrug resistance protein MRP1. Br J Pharmacol 126:681–688

64.	Leslie EM, Deeley RG, Cole SP (2001) Toxicological relevance of the multidrug resistance protein 1, MRP1 (ABCC1) and related transporters. Toxicology 167:3–23

65.	Loe DW, Deeley RG, Cole SP (1998) Characterization of vincristine transport by the M(r) 190, 000 multidrug resistance protein (MRP): evidence for cotransport with reduced glutathione. Cancer Res 58:5130–5136

66.	Salerno M, Garnier-Suillerot A (2001) Kinetics of glutathione and daunorubicin efflux from multidrug resistance protein overexpressing small-cell lung cancer cells. Eur J Pharmacol 421:1–9

67.	Leslie EM, Deeley RG, Cole SP (2003) Bioflavonoid stimulation of glutathione transport by the 190-kDa multidrug resistance protein 1 (MRP1). Drug Metab Dispos 31:11–15

68.	Leier I, Jedlitschky G, Buchholz U et al (1996) ATP-dependent glutathione disulphide transport mediated by the MRP gene-encoded conjugate export pump. Biochem J 314:433–437

69.	Loe DW, Deeley RG, Cole SP (2000) Verapamil stimulates glutathione transport by the 190-kDa multidrug resistance protein 1 (MRP1). J Pharmacol Exp Ther 293:530–538

70.	Jedlitschky G, Leier I, Buchholz U et al (1997) ATP-dependent transport of bilirubin glucuronides by the multidrug resistance protein MRP1 and its hepatocyte canalicular isoform MRP2. Biochem J 327(Pt 1):305–310

71.	Loe DW, Almquist KC, Cole SP, Deeley RG (1996) ATP-dependent 17 beta-estradiol 17-(beta-D-glucuronide) transport by multidrug resistance protein (MRP). Inhibition by cholestatic steroids. J Biol Chem 271:9683–9689

72.	Jedlitschky G, Leier I, Buchholz U, Center M, Keppler D (1994) ATP-dependent transport of glutathione S-conjugates by the multidrug resistance-associated protein. Cancer Res 54:4833–4836

73.	Leier I, Jedlitschky G, Buchholz U et al (1994) The MRP gene encodes an ATP-dependent export pump for leukotriene C4 and structurally related conjugates. J Biol Chem 269:27807–27810

74.	Muller M, Meijer C, Zaman GJ et al (1994) Overexpression of the gene encoding the multidrug resistance-associated protein results in increased ATP-dependent glutathione S-conjugate transport. Proc Natl Acad Sci USA 91:13033–13037

75.	Keppler D, Leier I, Jedlitschky G (1997) Transport of glutathione conjugates and glucuronides by the multidrug resistance proteins MRP1 and MRP2. Biol Chem 378:787–791

76.	Leier I, Jedlitschky G, Buchholz U, Keppler D (1994) Characterization of the ATP-dependent leukotriene C4 export carrier in mastocytoma cells. Eur J Biochem 220:599–606

77.	Wijnholds J, Evers R, van Leusden MR et al (1997) Increased sensitivity to anticancer drugs and decreased inflammatory response in mice lacking the multidrug resistance-associated protein. Nat Med 3:1275–1279

78.	Schroder O, Sjostrom M, Qiu H, Jakobsson PJ, Haeggstrom JZ (2005) Microsomal glutathione S-transferases: selective up-regulation of leukotriene C4 synthase during lipopolysaccharide-induced pyresis. Cell Mol Life Sci 62:87–94

79.	Shimada K, Navarro J, Goeger DE et al (1998) Expression and regulation of leukotriene-synthesis enzymes in rat liver cells. Hepatology 28:1275–1281

80.	Mayatepek E (2000) Leukotriene C4 synthesis deficiency: a member of a probably underdiagnosed new group of neurometabolic diseases. Eur J Pediatr 159:811–818

81.	Scoggan KA, Jakobsson PJ, Ford-Hutchinson AW (1997) Production of leukotriene C4 in different human tissues is attributable to distinct membrane bound biosynthetic enzymes. J Biol Chem 272:10182–10187

82.	Dekkers DW, Comfurius P, Schroit AJ, Bevers EM, Zwaal RF (1998) Transbilayer movement of NBD-labeled phospholipids in red blood cell membranes: outward-directed transport by the multidrug resistance protein 1 (MRP1). Biochemistry 37:14833–14837

83.	Borst P, Zelcer N, van Helvoort A (2000) ABC transporters in lipid transport. Biochim Biophys Acta 1486:128–144

84.	Dekkers DW, Comfurius P, van Gool RG, Bevers EM, Zwaal RF (2000) Multidrug resistance protein 1 regulates lipid asymmetry in erythrocyte membranes. Biochem J 350(Pt 2):531–535

85.	Raggers RJ, van Helvoort A, Evers R, van Meer G (1999) The human multidrug resistance protein MRP1 translocates sphingolipid analogs across the plasma membrane. J Cell Sci 112(Pt 3):415–422

86.	Mannechez A, Collet B, Payen L et al (2001) Differentiation of the Pgp and MRP1 multidrug resistance systems by mobile lipid 1H-NMR spectroscopy and phosphatidylserine externalization. Anticancer Res 21:3915–3919

87.	Kamp D, Haest CW (1998) Evidence for a role of the multidrug resistance protein (MRP) in the outward translocation of NBD-phospholipids in the erythrocyte membrane. Biochim Biophys Acta 1372:91–101

88.	Sohnius A, Kamp D, Haest CW (2003) ATP and GSH dependence of MRP1-mediated outward translocation of phospholipid analogs in the human erythrocyte membrane. Mol Membr Biol 20:299–305

89.	Huang Z, Chang X, Riordan JR, Huang Y (2004) Fluorescent modified phosphatidylcholine floppase activity of reconstituted multidrug resistance-associated protein MRP1. Biochim Biophys Acta 1660:155–163

90.	Lorico A, Rappa G, Finch RA et al (1997) Disruption of the murine MRP (multidrug resistance protein) gene leads to increased sensitivity to etoposide (VP-16) and increased levels of glutathione. Cancer Res 57:5238–5242

91.	Rappa G, Finch RA, Sartorelli AC, Lorico A (1999) New insights into the biology and pharmacology of the multidrug resistance protein (MRP) from gene knockout models. Biochem Pharmacol 58:557–562

92.	Rao VV, Dahlheimer JL, Bardgett ME et al (1999) Choroid plexus epithelial expression of MDR1 P glycoprotein and multidrug resistance-associated protein contribute to the blood-cerebrospinal-fluid drug-permeability barrier. Proc Natl Acad Sci USA 96:3900–3905

93.	Muller M, de Vries EG, Jansen PL (1996) Role of multidrug resistance protein (MRP) in glutathione S-conjugate transport in mammalian cells. J Hepatol 24:100–108

94.	Stride BD, Grant CE, Loe DW et al (1997) Pharmacological characterization of the murine and human orthologs of multidrug-resistance protein in transfected human embryonic kidney cells. Mol Pharmacol 52:344–353

95.	Gao M, Loe DW, Grant CE, Cole SPC, Deeley RG (1996) Reconstitution of ATP-dependent leukotriene C4 transport by Co-expression of both half-molecules of human multidrug resistance protein in insect cells. J Biol Chem 271:27782–27787

96.	Keppler D, Leier I, Jedlitschky G, Mayer R, Buchler M (1996) The function of the multidrug resistance proteins (MRP and cMRP) in drug conjugate transport and hepatobiliary excretion. Adv Enzyme Regul 36:17–29

97.	Lautier D, Canitrot Y, Deeley RG, Cole SP (1996) Multidrug resistance mediated by the multidrug resistance protein (MRP) gene. Biochem Pharmacol 52:967–977

98.	Ren XQ, Furukawa T, Aoki S et al (2001) Glutathione-dependent binding of a photoaffinity analog of agosterol A to the C-terminal half of human multidrug resistance protein. J Biol Chem 276:23197–23206

99.	Payen L, Gao M, Westlake C et al (2005) Functional interactions between nucleotide binding domains and leukotriene C4 binding sites of multidrug resistance protein 1 (ABCC1). Mol Pharmacol 67:1944–1953

100.	Payen LF, Gao M, Westlake CJ, Cole SP, Deeley RG (2003) Role of carboxylate residues adjacent to the conserved core Walker B motifs in the catalytic cycle of multidrug resistance protein 1 (ABCC1). J Biol Chem 278:38537–38547

101.	Qian YM, Qiu W, Gao M et al (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. J Biol Chem 276:38636–38644

102.	Karwatsky J, Leimanis M, Cai J, Gros P, Georges E (2005) The leucotriene C4 binding sites in multidrug resistance protein 1 (ABCC1) include the first membrane multiple spanning domain. Biochemistry 44:340–351

103.	Qian YM, Grant CE, Westlake CJ et al (2002) Photolabeling of human and murine multidrug resistance protein 1 with the high affinity inhibitor (125I)LY475776 and azidophenacyl-(35S)glutathione. J Biol Chem 277:35225–35231

104.	Mao Q, Qiu W, Weigl KE et al (2002) GSH-dependent photolabeling of multidrug resistance protein MRP1 (ABCC1) by (125I)LY475776. Evidence of a major binding site in the COOH-proximal membrane spanning domain. J Biol Chem 277:28690–28699

105.	Daoud R, Desneves J, Deady LW et al (2000) The multidrug resistance protein is photoaffinity labeled by a quinoline-based drug at multiple sites. Biochemistry 39:6094–6102

106.	Daoud R, Kast C, Gros P, Georges E (2000) Rhodamine 123 binds to multiple sites in the multidrug resistance protein (MRP1). Biochemistry 39:15344–15352

107.	Daoud R, Julien M, Gros P, Georges E (2001) Major photoaffinity drug binding sites in multidrug resistance protein 1 (MRP1) are within transmembrane domains 10–11 and 16–17. J Biol Chem 276:12324–12330

108.	Greenberger LM (1993) Major photoaffinity drug labeling sites for iodoaryl azidoprazosin in P-glycoprotein are within, or immediately C-terminal to, transmembrane domains 6 and 12. J Biol Chem 268:11417–11425

109.	Loo TW, Clarke DM (1997) Identification of residues in the drug-binding site of human P-glycoprotein using a thiol-reactive substrate. J Biol Chem 272:31945–31948

110.	Dey S, Ramachandra M, Pastan I, Gottesman MM, Ambudkar SV (1997) Evidence for two nonidentical drug-interaction sites in the human P-glycoprotein. Proc Natl Acad Sci USA 94:10594–10599

111.	Shapiro AB, Fox K, Lam P, Ling V (1999) Stimulation of P-glycoprotein-mediated drug transport by prazosin and progesterone. Evidence for a third drug-binding site. Eur J Biochem 259:841–850

112.	Leslie EM, Letourneau IJ, Deeley RG, Cole SP (2003) Functional and structural consequences of cysteine substitutions in the NH2 proximal region of the human multidrug resistance protein 1 (MRP1/ABCC1). Biochemistry 42:5214–5224

113.	Koike K, Conseil G, Leslie EM, Deeley RG, Cole SP (2004) Identification of proline residues in the core cytoplasmic and transmembrane regions of multidrug resistance protein 1 (MRP1/ABCC1) important for transport function, substrate specificity, and nucleotide interactions. J Biol Chem 279:12325–12336

114.	Haimeur A, Deeley RG, Cole SP (2002) Charged amino acids in the sixth transmembrane helix of multidrug resistance protein 1 (MRP1/ABCC1) are critical determinants of transport activity. J Biol Chem 277:41326–41333

115.	Koike K, Oleschuk CJ, Haimeur A et al (2002) Multiple membrane-associated tryptophan residues contribute to the transport activity and substrate specificity of the human multidrug resistance protein, MRP1. J Biol Chem 277:49495–49503

116.	Zhang DW, Nunoya K, Vasa M et al (2006) Mutational analysis of polar amino acid residues within predicted transmembrane helices 10 and 16 of multidrug resistance protein 1 (ABCC1): effect on substrate specificity. Drug Metab Dispos 34:539–546

117.	Zhang DW, Nunoya K, Vasa M et al (2004) Transmembrane helix 11 of multidrug resistance protein 1 (MRP1/ABCC1): identification of polar amino acids important for substrate specificity and binding of ATP at nucleotide binding domain 1. Biochemistry 43:9413–9425

118.	Campbell JD, Koike K, Moreau C et al (2004) Molecular modeling correctly predicts the functional importance of Phe594 in transmembrane helix 11 of the multidrug resistance protein, MRP1 (ABCC1). J Biol Chem 279:463–468

119.	Zhang DW, Cole SP, Deeley RG (2001) Identification of an amino acid residue in multidrug resistance protein 1 critical for conferring resistance to anthracyclines. J Biol Chem 276:13231–13239

120.	Zhang DW, Gu HM, Situ D et al (2003) Functional importance of polar and charged amino acid residues in transmembrane helix 14 of multidrug resistance protein 1 (MRP1/ABCC1): identification of an aspartate residue critical for conversion from a high to low affinity substrate binding state. J Biol Chem 278:46052–46063

121.	Situ D, Haimeur A, Conseil G et al (2004) Mutational analysis of ionizable residues proximal to the cytoplasmic interface of membrane spanning domain 3 of the multidrug resistance protein, MRP1 (ABCC1): glutamate 1204 is important for both the expression and catalytic activity of the transporter. J Biol Chem 279:38871–38880

122.	Ito K, Olsen SL, Qiu W, Deeley RG, Cole SP (2001) Mutation of a single conserved tryptophan in multidrug resistance protein 1 (MRP1/ABCC1) results in loss of drug resistance and selective loss of organic anion transport. J Biol Chem 276:15616–15624

123.	Zhang DW, Cole SP, Deeley RG (2001) Identification of a nonconserved amino acid residue in multidrug resistance protein 1 important for determining substrate specificity: evidence for functional interaction between transmembrane helices 14 and 17. J Biol Chem 276:34966–34974

124.	Zhang DW, Cole SP, Deeley RG (2002) Determinants of the substrate specificity of multidrug resistance protein 1: role of amino acid residues with hydrogen bonding potential in predicted transmembrane helix 17. J Biol Chem 277:20934–20941

125.	Stride BD, Cole SP, Deeley RG (1999) Localization of a substrate specificity domain in the multidrug resistance protein. J Biol Chem 274:22877–22883

126.	Karwatsky J, Daoud R, Cai J, Gros P, Georges E (2003) Binding of a photoaffinity analogue of glutathione to MRP1 (ABCC1) within two cytoplasmic regions (L0 and L1) as well as transmembrane domains 10–11 and 16–17. Biochemistry 42:3286–3294

127.	Karwatsky JM, Georges E (2004) Drug binding domains of MRP1 (ABCC1) as revealed by photoaffinity labeling. Curr Med Chem Anticancer Agents 4:19–30

128.	Bakos E, Evers R, Calenda G et al (2000) Characterization of the amino-terminal regions in the human multidrug resistance protein (MRP1). J Cell Sci 113(Pt 24):4451–4461

129.	Leslie EM, Ito K, Upadhyaya P et al (2001) Transport of the beta -O-glucuronide conjugate of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) by the multidrug resistance protein 1 (MRP1). Requirement for glutathione or a non-sulfur-containing analog. J Biol Chem 276:27846–27854

130.	Qian YM, Song WC, Cui H, Cole SP, Deeley RG (2001) Glutathione stimulates sulfated estrogen transport by multidrug resistance protein 1. J Biol Chem 276:6404–6411

131.	Buyse F, Hou YX, Vigano C et al (2006) Replacement of the positively charged Walker A lysine residue with a hydrophobic leucine residue and conformational alterations caused by this mutation in MRP1 impair ATP binding and hydrolysis. Biochem J 397:121–130

132.	Manciu L, Chang XB, Riordan JR, Ruysschaert JM (2000) Multidrug resistance protein MRP1 reconstituted into lipid vesicles: secondary structure and nucleotide-induced tertiary structure changes. Biochemistry 39:13026–13033

133.	Manciu L, Chang XB, Riordan JR, Buyse F, Ruysschaert JM (2001) Nucleotide-induced conformational changes in the human multidrug resistance protein MRP1 are related to the capacity of chemotherapeutic drugs to accumulate or not in resistant cells. FEBS Lett 493:31–35

134.	Taguchi Y, Yoshida A, Takada Y, Komano T, Ueda K (1997) Anti-cancer drugs and glutathione stimulate vanadate-induced trapping of nucleotide in multidrug resistance-associated protein (MRP). FEBS Lett 401:11–14

135.	Nagata K, Nishitani M, Matsuo M et al (2000) Nonequivalent nucleotide trapping in the two nucleotide binding folds of the human multidrug resistance protein MRP1. J Biol Chem 275:17626–17630

136.	Hou Y, Cui L, Riordan JR, Chang XB (2000) Allosteric interactions between the two non-equivalent nucleotide binding domains of multidrug resistance protein MRP1. J Biol Chem 275:20280–20287

137.	Leslie EM, Mao Q, Oleschuk CJ, Deeley RG, Cole SP (2001) Modulation of multidrug resistance protein 1 (MRP1/ABCC1) transport and atpase activities by interaction with dietary flavonoids. Mol Pharmacol 59:1171–1180

138.	Mao Q, Leslie EM, Deeley RG, Cole SP (1999) ATPase activity of purified and reconstituted multidrug resistance protein MRP1 from drug-selected H69AR cells. Biochim Biophys Acta 1461:69–82

139.	Chang XB, Hou YX, Riordan JR (1997) ATPase activity of purified multidrug resistance-associated protein (published erratum appears in J Biol Chem 1998 Mar 27;273(13):7782). J Biol Chem 272:30962–30968

140.	Manciu L, Chang XB, Buyse F et al (2003) Intermediate structural states involved in MRP1-mediated drug transport. Role of glutathione. J Biol Chem 278:3347–3356

141.	Smith PC, Karpowich N, Millen L et al (2002) ATP binding to the motor domain from an ABC transporter drives formation of a nucleotide sandwich dimer. Mol Cell 10:139–149

142.	Chen J, Lu G, Lin J, Davidson AL, Quiocho FA (2003) A tweezers-like motion of the ATP-binding cassette dimer in an ABC transport cycle. Mol Cell 12:651–661

143.	Moody JE, Millen L, Binns D, Hunt JF, Thomas PJ (2002) Cooperative, ATP-dependent association of the nucleotide binding cassettes during the catalytic cycle of ATP-binding cassette transporters. J Biol Chem 277:21111–21114

144.	Verdon G, Albers SV, Dijkstra BW, Driessen AJ, Thunnissen AM (2003) Crystal structures of the ATPase subunit of the glucose ABC transporter from Sulfolobus solfataricus: nucleotide-free and nucleotide-bound conformations. J Mol Biol 330:343–358

145.	Locher KP, Lee AT, Rees DC (2002) The E. coli BtuCD structure: a framework for ABC transporter architecture and mechanism. Science 296:1091–1098

146.	Rosenberg MF, Mao Q, Holzenburg A et al (2001) The structure of the multidrug resistance protein 1 (MRP1/ABCC1). crystallization and single-particle analysis. J Biol Chem 276:16076–16082

147.	Cool RH, Veenstra MK, van Klompenburg W et al (2002) S-decyl-glutathione nonspecifically stimulates the ATPase activity of the nucleotide-binding domains of the human multidrug resistance-associated protein, MRP1 (ABCC1). Eur J Biochem 269:3470–3478

148.	Kern A, Felfoldi F, Sarkadi B, Varadi A (2000) Expression and characterization of the N- and C-terminal ATP-binding domains of MRP1. Biochem Biophys Res Commun 273:913–919

149.	Ramaen O, Sizun C, Pamlard O, Jacquet E, Lallemand JY (2005) Attempts to characterize the NBD heterodimer of MRP1: transient complex formation involves Gly771 of the ABC signature sequence but does not enhance the intrinsic ATPase activity. Biochem J 391:481–490

150.	Ramaen O, Leulliot N, Sizun C et al (2006) Structure of the human multidrug resistance protein 1 nucleotide binding domain 1 bound to Mg2+/ATP reveals a non-productive catalytic site. J Mol Biol 359:940–949

151.	Szentpetery Z, Sarkadi B, Bakos E, Varadi A (2004) Functional studies on the MRP1 multidrug transporter: characterization of ABC-signature mutant variants. Anticancer Res 24:449–455

152.	Szentpetery Z, Kern A, Liliom K et al (2004) The role of the conserved glycines of ATP-binding cassette signature motifs of MRP1 in the communication between the substrate-binding site and the catalytic centers. J Biol Chem 279:41670–41678

153.	Ren XQ, Furukawa T, Haraguchi M et al (2004) Function of the ABC signature sequences in the human multidrug resistance protein 1. Mol Pharmacol 65:1536–1542

154.	Pascaud C, Garrigos M, Orlowski S (1998) Multidrug resistance transporter P-glycoprotein has distinct but interacting binding sites for cytotoxic drugs and reversing agents. Biochem J 333(Pt 2):351–358

155.	Martin C, Berridge G, Higgins CF et al (2000) Communication between multiple drug binding sites on P-glycoprotein. Mol Pharmacol 58:624–632

156.	Yang R, McBride A, Hou YX, Goldberg A, Chang XB (2005) Nucleotide dissociation from NBD1 promotes solute transport by MRP1. Biochim Biophys Acta 1668:248–261

157.	Yang R, Scavetta R, Chang XB (2008) Interaction between the bound Mg.ATP and the Walker A serine residue in NBD2 of multidrug resistance-associated protein MRP1 plays a crucial role for the ATP-dependent leukotriene C4 transport. Biochemistry 47:8456–8464

158.	Hou YX, Cui L, Riordan JR, Chang XB (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. J Biol Chem 277:5110–5119

159.	Hou YX, Riordan JR, Chang XB (2003) ATP binding, not hydrolysis, at the first nucleotide-binding domain of multidrug resistance-associated protein MRP1 enhances ADP.Vi trapping at the second domain. J Biol Chem 278:3599–3605

160.	Zhao Q, Chang XB (2004) Mutation of the aromatic amino acid interacting with adenine moiety of ATP to a polar residue alters the properties of multidrug resistance protein 1. J Biol Chem 279:48505–48512

161.	Chang XB (2007) A molecular understanding of ATP-dependent solute transport by multidrug resistance-associated protein MRP1. Cancer Metastasis Rev 26:15–37

162.	Senior AE (1998) Catalytic mechanism of P-glycoprotein. Acta Physiol Scand Suppl 643:213–218

163.	Senior AE, al-Shawi MK, Urbatsch IL (1998) ATPase activity of Chinese hamster P-glycoprotein. Methods Enzymol 292:514–523

164.	Urbatsch IL, Sankaran B, Weber J, Senior AE (1995) P-glycoprotein is stably inhibited by vanadate-induced trapping of nucleotide at a single catalytic site. J Biol Chem 270:19383–19390

165.	Urbatsch IL, Sankaran B, Bhagat S, Senior AE (1995) Both P-glycoprotein nucleotide-binding sites are catalytically active. J Biol Chem 270:26956–26961

166.	Senior AE, Bhagat S (1998) P-glycoprotein shows strong catalytic cooperativity between the two nucleotide sites. Biochemistry 37:831–836

167.	Carrier I, Julien M, Gros P (2003) Analysis of catalytic carboxylate mutants E552Q and E1197Q suggests asymmetric ATP hydrolysis by the two nucleotide-binding domains of P-glycoprotein. Biochemistry 42:12875–12885

168.	Urbatsch IL, Beaudet L, Carrier I, Gros P (1998) Mutations in either nucleotide-binding site of P-glycoprotein (Mdr3) prevent vanadate trapping of nucleotide at both sites. Biochemistry 37:4592–4602

169.	Urbatsch IL, Julien M, Carrier I et al (2000) Mutational analysis of conserved carboxylate residues in the nucleotide binding sites of P-glycoprotein. Biochemistry 39:14138–14149

170.	Azzaria M, Schurr E, Gros P (1989) Discrete mutations introduced in the predicted nucleotide-binding sites of the mdr1 gene abolish its ability to confer multidrug resistance. Mol Cell Biol 9:5289–5297

171.	Senior AE, al-Shawi MK, Urbatsch IL (1995) The catalytic cycle of P-glycoprotein. FEBS Lett 377:285–289

172.	Sauna ZE, Ambudkar SV (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. J Biol Chem 276:11653–11661

173.	Sauna ZE, Ambudkar SV (2000) Evidence for a requirement for ATP hydrolysis at two distinct steps during a single turnover of the catalytic cycle of human P-glycoprotein. Proc Natl Acad Sci USA 97:2515–2520

174.	Yang R, Scavetta R, Chang XB (2008) The hydroxyl group of S685 in Walker A motif and the carboxyl group of D792 in Walker B motif of NBD1 play a crucial role for multidrug resistance protein folding and function. Biochim Biophys Acta 1778:454–465

175.	Cui L, Hou YX, Riordan JR, Chang XB (2001) Mutations of the Walker B motif in the first nucleotide binding domain of multidrug resistance protein MRP1 prevent conformational maturation. Arch Biochem Biophys 392:153–161

176.	Yang R, Cui L, Hou Y-X, Riordan JR, Chang XB (2003) ATP binding to the first nucleotide binding domain of multidrug resistance-associated protein plays a regulatory role at low nucleotide concentration, whereas ATP hydrolysis at the second plays a dominant role in ATP-dependent leukotriene C4 transport. J Biol Chem 278:30764–30771

177.	Hung LW, Wang IX, Nikaido K et al (1998) Crystal structure of the ATP-binding subunit of an ABC transporter. Nature 396:703–707

178.	Lu G, Westbrooks JM, Davidson AL, Chen J (2005) ATP hydrolysis is required to reset the ATP-binding cassette dimer into the resting-state conformation. Proc Natl Acad Sci USA 102:17969–17974

179.	Hopfner KP, Karcher A, Shin DS et al (2000) Structural biology of Rad50 ATPase: ATP-driven conformational control in DNA double-strand break repair and the ABC-ATPase superfamily. Cell 101:789–800

180.	Diederichs K, Diez J, Greller G et al (2000) Crystal structure of MalK, the ATPase subunit of the trehalose/maltose ABC transporter of the archaeon Thermococcus litoralis. EMBO J 19:5951–5961

181.	Zaitseva J, Jenewein S, Jumpertz T, Holland IB, Schmitt L (2005) H662 is the linchpin of ATP hydrolysis in the nucleotide-binding domain of the ABC transporter HlyB. EMBO J 24:1901–1910

182.	Ernst R, Kueppers P, Klein CM et al (2008) A mutation of the H-loop selectively affects rhodamine transport by the yeast multidrug ABC transporter Pdr5. Proc Natl Acad Sci USA 105:5069–5074

183.	Shyamala V, Baichwal V, Beall E, Ames GF (1991) Structure-function analysis of the histidine permease and comparison with cystic fibrosis mutations. J Biol Chem 266:18714–18719

184.	Davidson AL, Sharma S (1997) Mutation of a single MalK subunit severely impairs maltose transport activity in Escherichia coli. J Bacteriol 179:5458–5464

185.	Nikaido K, Ames GF (1999) One intact ATP-binding subunit is sufficient to support ATP hydrolysis and translocation in an ABC transporter, the histidine permease. J Biol Chem 274:26727–26735

186.	Yang R, Chang XB (2007) Hydrogen-bond formation of the residue in H-loop of the nucleotide binding domain 2 with the ATP in this site and/or other residues of multidrug resistance protein MRP1 plays a crucial role during ATP-dependent solute transport. Biochim Biophys Acta 1768:324–335

187.	Dawson RJ, Locher KP (2006) Structure of a bacterial multidrug ABC transporter. Nature 443:180–185

188.	Pinkett HW, Lee AT, Lum P, Locher KP, Rees DC (2007) An inward-facing conformation of a putative metal-chelate-type ABC transporter. Science 315:373–377

189.	Oldham ML, Khare D, Quiocho FA, Davidson AL, Chen J (2007) Crystal structure of a catalytic intermediate of the maltose transporter. Nature 450:515–521

190.	Ward A, Reyes CL, Yu J, Roth CB, Chang G (2007) Flexibility in the ABC transporter MsbA: alternating access with a twist. Proc Natl Acad Sci USA 104:19005–19010

191.	Trompier D, Chang XB, Barattin R et al (2004) Verapamil and its derivative trigger apoptosis through glutathione extrusion by multidrug resistance protein MRP1. Cancer Res 64:4950–4956

192.	Perrotton T, Trompier D, Chang XB, Di Pietro A, Baubichon-Cortay H (2007) (R)- and (S)-verapamil differentially modulate the multidrug-resistant protein MRP1. J Biol Chem 282:31542–31548

193.	Salerno M, Loechariyakul P, Saengkhae C, Garnier-Suillerot A (2004) Relation between the ability of some compounds to modulate the MRP1-mediated efflux of glutathione and to inhibit the MRPl-mediated efflux of daunorubicin. Biochem Pharmacol 68:2159–2165

194.	Cole SP, Downes HF, Mirski SE, Clements DJ (1990) Alterations in glutathione and glutathione-related enzymes in a multidrug-resistant small cell lung cancer cell line. Mol Pharmacol 37:192–197

195.	Campling BG, Baer K, Baker HM, Lam YM, Cole SP (1993) Do glutathione and related enzymes play a role in drug resistance in small cell lung cancer cell lines? Br J Cancer 68:327–335

196.	Rappa G, Gamcsik MP, Mitina RL et al (2003) Retroviral transfer of MRP1 and gamma-glutamyl cysteine synthetase modulates cell sensitivity to L-buthionine-S, R-sulphoximine (BSO): new rationale for the use of BSO in cancer therapy. Eur J Cancer 39:120–128

197.	Zaman GJ, Lankelma J, van Tellingen O et al (1995) Role of glutathione in the export of compounds from cells by the multidrug-resistance-associated protein. Proc Natl Acad Sci USA 92:7690–7694

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