IUBMB Enzyme Nomenclature

EC 3.6.3.44

Accepted name: xenobiotic-transporting ATPase

Reaction: ATP + H2O + xenobioticin = ADP + phosphate + xenobioticout

Other name(s): multidrug-resistance protein; MDR protein; P-glycoprotein; pleiotropic-drug-resistance protein; PDR protein; steroid-transporting ATPase; ATP phosphohydrolase (steroid-exporting)

Systematic name: ATP phosphohydrolase (xenobiotic-exporting)

Comments: ABC-type (ATP-binding cassette-type) ATPase, characterized by the presence of two similar ATP-binding domains. Does not undergo phosphorylation during the transport process. The enzyme from Gram-positive bacteria and eukaryotic cells export a number of drugs, with unusual specificity, covering various groups of unrelated substances, while ignoring some that are closely related structurally. Several distinct enzymes may be present in a single eukaryotic cell. Many of them transport glutathione—drug conjugates. Some also show some 'flippase' (phospholipid-translocating ATPase; EC 3.6.3.1) activity.

Links to other databases: BRENDA, EXPASY, KEGG Metacyc, PDB, CAS registry number:

References:

1. Bellamy, W.T. P-glycoproteins and multidrug resistance. Annu. Rev. Pharmac. Toxicol. 36 (1996) 161-183. [PMID: 8725386]

2. Frijters, C.M., Ottenhoff, R., Van Wijland, M.J., Van Nieuwkerk, C., Groen, A.K. and Oude-Elferink, R.P. Influence of bile salts on hepatic mdr2 P-glycoprotein expression. Adv. Enzyme Regul. 36 (1996) 351-363. [PMID: 8869755]

3. Keppler, D., König, J. and Buchler, M. The canalicular multidrug resistance protein, cMRP/MRP2, a novel conjugate export pump expressed in the apical membrane of hepatocytes. Adv. Enzyme Regul. 37 (1997) 321-333. [PMID: 9381978]

4. Loe, D.W., Deeley, R.G. and Cole, S.P. Characterization of vincristine transport by the Mr 190,000 multidrug resistance protein (MRP): evidence for cotransport with reduced glutathione. Cancer Res. 58 (1998) 5130-5136. [PMID: 9823323]

5. van Veen, H.W. and Konings, W.N. The ABC family of multidrug transporters in microorganisms. Biochim. Biophys. Acta 1365 (1998) 31-36. [PMID: 9693718]

6. Griffiths, J.K. and Sansom, C.E. (Ed.), The Transporter Factsbook, Academic Press, San Diego, 1998,

7. Prasad, R., De Wergifosse, P., Goffeau, A. and Balzi, E. Molecular cloning and characterization of a novel gene of Candida albicans, CDR1, conferring multiple resistance to drugs and antifungals. Curr. Genet. 27 (1995) 320-329. [PMID: 7614555]

8. Nagao, K., Taguchi, Y., Arioka, M., Kadokura, H., Takatsuki, A., Yoda, K. and Yamasaki, M. bfr1+, a novel gene of Schizosaccharomyces pombe which confers brefeldin A resistance, is structurally related to the ATP-binding cassette superfamily. J. Bacteriol. 177 (1995) 1536-1543. [PMID: 7883711]

9. Mahé, Y., Lemoine, Y. and Kuchler, K. The ATP-binding cassette transporters Pdr5 and Snq2 of Saccharomyces cerevisiae can mediate transport of steroids in vivo. J. Biol. Chem. 271 (1996) 25167-25172. [PMID: 8810273]

[EC 3.6.3.44 created 2000 (EC 3.6.3.45 incorporated 2006), modified 2006]


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