Characterization of the Role of Polar Amino Acid Residues within Predicted Transmembrane Helix 17 in Determining the Substrate Specificity of Multidrug Resistance Protein 3†

Biochemistry ◽  
2003 ◽  
Vol 42 (33) ◽  
pp. 9989-10000 ◽  
Author(s):  
Da-Wei Zhang ◽  
Hong-Mei Gu ◽  
Monika Vasa ◽  
Mario Muredda ◽  
Susan P. C. Cole ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Amino Acid ◽  
Transmembrane Helix ◽  
Multidrug Resistance Protein ◽  
Amino Acid Residues ◽  
Polar Amino Acid ◽  
Multidrug Resistance Protein 3 ◽  
Resistance Protein

scholarly journals Functional Role of Arginine 375 in Transmembrane Helix 6 of Multidrug Resistance Protein 4 (MRP4/ABCC4)

2008 ◽  
Vol 74 (4) ◽  
pp. 964-971 ◽  
Author(s):  
Azza A. K. El-Sheikh ◽  
Jeroen J. M. W. van den Heuvel ◽  
Elmar Krieger ◽  
Frans G. M. Russel ◽  
Jan B. Koenderink
Keyword(s):  
Multidrug Resistance ◽  
Functional Role ◽  
Transmembrane Helix ◽  
Multidrug Resistance Protein ◽  
Resistance Protein

Substitution of Trp1242 of TM17 alters substrate specificity of human multidrug resistance protein 3

2003 ◽  
Vol 284 (2) ◽  
pp. G280-G289 ◽  
Author(s):  
Curtis J. Oleschuk ◽  
Roger G. Deeley ◽  
Susan P. C. Cole
Keyword(s):  
Multidrug Resistance ◽  
Substrate Specificity ◽  
Multidrug Resistance Protein ◽  
Wild Type ◽  
Multidrug Resistance Protein 3 ◽  
17Β Estradiol ◽  
Resistance Protein ◽  
Estradiol 17Β ◽  
Taurocholate Transport

Multidrug resistance protein 3 (MRP3) is an ATP-dependent transporter of 17β-estradiol 17β(d-glucuronide) (E217βG), leukotriene C4 (LTC4), methotrexate, and the bile salts taurocholate and glycocholate. In the present study, the role of a highly conserved Trp residue at position 1242 on MRP3 transport function was examined by expressing wild-type MRP3 and Ala-, Cys-, Phe-, Tyr-, and Pro-substituted mutants in human embryonic kidney 293T cells. Four MRP3-Trp1242 mutants showed significantly increased E217βG uptake, whereas transport by the Pro mutant was undetectable. Similarly, the Pro mutant did not transport LTC4. By comparison, LTC4transport by the Ala, Cys, Phe, and Tyr mutants was reduced by ∼35%. The Ala, Cys, Phe, and Tyr mutants all showed greatly reduced methotrexate and leucovorin transport, except the Tyr mutant, which transported leucovorin at levels comparable with wild-type MRP3. In contrast, the MRP3-Trp1242 substitutions did not significantly affect taurocholate transport or taurocholate and glycocholate inhibition of E217βG uptake. Thus Trp1242 substitutions markedly alter the substrate specificity of MRP3 but leave bile salt binding and transport intact.

scholarly journals Role of Multidrug Resistance Protein 3 in Antifungal-Induced Cholestasis

2016 ◽  
Vol 90 (1) ◽  
pp. 23-34 ◽  
Author(s):  
Zainab M. Mahdi ◽  
Uta Synal-Hermanns ◽  
Aylin Yoker ◽  
Kaspar P. Locher ◽  
Bruno Stieger
Keyword(s):  
Multidrug Resistance ◽  
Multidrug Resistance Protein ◽  
Multidrug Resistance Protein 3 ◽  
Resistance Protein
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