ABCC1 p.His1486Asp

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PMID: 17187755 [PubMed] Yang R et al: "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."
No. Sentence Comment
43 In addition, the following mutations as shown in Fig. 5A (H827D, H1486D, H827D/ H1486D, H827N, H1486N, H827N/H1486N, H827E, H1486E, H827E/ H1486E, H827Q, H1486Q, H827Q/H1486Q, H827Y, H1486Y, H827Y/ H1486Y, H827W, H1486W and H827W/H1486W) were also introduced into the full length MRP1 cDNA by using the following primers: H827D/forward, 5'-CGG ATC TTG GTC ACG GAC AGC ATG AGC TAC TTG-3'; H827D/ reverse, 5'-CAA GTA GCT CAT GCT GTC CGT GAC CAA GAT CCG-3'; H1486D/forward, 5'-GTC CTC ACC ATC GCC GAC CGG CTC AAC ACC ATC-3'; H1486D/reverse, 5'-GAT GGT GTT GAG CCG GTC GGC GAT GGT GAG GAC-3'; H827N/forward, 5'-CGG ATC TTG GTC ACG AAC AGC ATG AGC TAC TTG-3'; H827N/reverse, 5'-CAA GTA GCT CAT GCT GTT CGT GAC CAA GAT CCG-3'; H1486N/forward, 5'-GTC CTC ACC ATC GCC AAC CGG CTC AAC ACC ATC-3'; H1486N/reverse, 5'-GAT GGT GTT GAG CCG GTT GGC GAT GGT GAG GAC-3'; H827E/forward, 5'-CGG ATC TTG GTC ACG GAG AGC ATG AGC TAC TTG-3'; H827E/reverse, 5'-CAA GTA GCT CAT GCT CTC CGT GAC CAA GAT CCG-3'; H1486E/forward, 5'-GTC CTC ACC ATC GCC GAG CGG CTC AAC ACC ATC-3'; H1486E/reverse, 5'-GAT GGT GTT GAG CCG CTC GGC GAT GGT GAG GAC-3'; H827Q/forward, 5'- CGG ATC TTG GTC ACG CAG AGC ATG AGC TAC TTG-3'; H827Q/ reverse, 5'-CAA GTA GCT CAT GCT CTG CGT GAC CAA GAT CCG-3'; H1486Q/forward, 5'-GTC CTC ACC ATC GCC CAG CGG CTC AAC ACC ATC-3'; H1486Q/reverse, 5'-GAT GGT GTT GAG CCG CTG GGC GAT GGT GAG GAC-3'; H827Y/forward, 5'-CGG ATC TTG GTC ACG TAC AGC ATG AGC TAC TTG-3'; H827Y/reverse, 5'-CAA GTA GCT CAT GCT GTA CGT GAC CAA GAT CCG-3'; H1486Y/forward, 5'-GTC CTC ACC ATC GCC TAC CGG CTC AAC ACC ATC-3'; H1486Y/reverse, 5'-GAT GGT GTT GAG CCG GTA GGC GAT GGT GAG GAC-3'; H827W/forward, 5'-CGG ATC TTG GTC ACG TGG AGC ATG AGC TAC TTG-3'; H827W/reverse, 5'-CAA GTA GCT CAT GCT CCA CGT GAC CAA GAT CCG-3'; H1486W/forward, 5'-GTC CTC ACC ATC GCC TGG CGG CTC AAC ACC ATC-3'; H1486W/reverse, 5'-GAT GGT GTT GAG CCG CCA GGC GAT GGT GAG GAC-3'.
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ABCC1 p.His1486Asp 17187755:43:65
status: NEW
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ABCC1 p.His1486Asp 17187755:43:80
status: NEW
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ABCC1 p.His1486Asp 17187755:43:455
status: NEW
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ABCC1 p.His1486Asp 17187755:43:522
status: NEW
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164 In order to test this hypothesis, H827D, H1486D, H827D/H1486D, H827N, H1486N, H827N/H1486N, H827E, H1486E, H827E/H1486E, H827Q, H1486Q, H827Q/H1486Q, H827Y, H1486Y, H827Y/ H1486Y, H827W, H1486W and H827W/H1486W mutations (Fig. 5A) were introduced into full length of MRP1 cDNA in pNUT/MRP1/His and expressed in BHK cells at 37 °C.
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ABCC1 p.His1486Asp 17187755:164:41
status: NEW
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ABCC1 p.His1486Asp 17187755:164:55
status: NEW
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169 H1486N had ~60% of wild-type MRP1 transport activity, whereas H1486D dropped this activity to ~20%.
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ABCC1 p.His1486Asp 17187755:169:62
status: NEW
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210 In contrast, mutations in NBD2, such as H1486L, H1486F, H1486D, H1486N, H1486E, H1486Q, H1486Y and H1486W, have variant effects on the ATP-dependent LTC4 transport (Figs. 1C, 4B and 5C)).
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ABCC1 p.His1486Asp 17187755:210:56
status: NEW
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225 The transport activity of H1486D dropped from ~36% (H1486E) to ~20% (Fig. 5C), consistent with the above conclusion.
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ABCC1 p.His1486Asp 17187755:225:26
status: NEW
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