ABCC1 p.Arg1138Lys

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PMID: 16230346 [PubMed] Conseil G et al: "Functional importance of three basic residues clustered at the cytosolic interface of transmembrane helix 15 in the multidrug and organic anion transporter MRP1 (ABCC1)."
No. Sentence Comment
47 Substitutions of charged residues were generated in the pGEM-3Z- XmaI/MRP1 plasmid according to the manufacturer`s instructions with the following mutagenic primers (Integrated DNA Technologies, Inc., Coralville, IA), which also introduced an additional silent restriction site (substituted nucleotides are underlined): R1138E, 5Ј-CGT GGC TTC CTC CGA GCA ACT GAA GCG CCT CGA G-3Ј; R1138K, 5Ј-CGT GGC TTC CTC CAA GCA GCT TAA GCG CCT CGA G-3Ј; K1141E, 5Ј-CGG CAG CTG GAG CGC CTG GAG TCG GTC AGC-3Ј; K1141R, 5Ј-CCC GGC AGC TGC GGC GCC TCG AGT CGG-3Ј; R1142E, 5Ј-CCC GGC AGC TGA AGG AGC TCG AGT CGG TCA GCC G-3Ј;R1142K, 5Ј-CCC GGC AGC TGA AGA AGC TTG AGT CGG TCA GCC G-3Ј.
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ABCC1 p.Arg1138Lys 16230346:47:393
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122 B, HEK293T cells were transfected with expression vectors encoding WT-MRP1 and MRP1 mutants R1138E, R1138K, K1141E, K1141R, R1142E, and R1142K, and 48 h later, cells were probed with monoclonal antibody QCRL-3 and processed for confocal fluorescence microscopy using Alexa Fluor 488 conjugated secondary antibody.
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ABCC1 p.Arg1138Lys 16230346:122:100
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138 On the other hand, LTC4 labeling of the R1138K mutant and both Arg1142 mutants was comparable with wild-type MRP1, although these mutants had very low LTC4 transport activity (Ͻ10-40% wild type).
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ABCC1 p.Arg1138Lys 16230346:138:40
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139 Therefore, reduced substrate binding appeared to explain, at least in part, the loss of LTC4 transport for the R1138E and K1141E mutants but not the R1138K, R1142E, and R1142K mutants.
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ABCC1 p.Arg1138Lys 16230346:139:149
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200 The reduction in GSH and LTC4 transport appeared largely attributable to a substantial decrease in substrate binding in the case of R1138E but not R1138K.
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ABCC1 p.Arg1138Lys 16230346:200:147
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PMID: 21143116 [PubMed] He SM et al: "Structural and functional properties of human multidrug resistance protein 1 (MRP1/ABCC1)."
No. Sentence Comment
744 The Arg1138Glu and Lys1141Glu mutants, but not the Arg1138Lys, Arg1142Glu, and Arg1142Lys mutants, showed a >50% decrease in binding to [3 H]LTC4.
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ABCC1 p.Arg1138Lys 21143116:744:51
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