ABCB1 p.Trp803Ala

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PMID: 8995353 [PubMed] Loo TW et al: "Correction of defective protein kinesis of human P-glycoprotein mutants by substrates and modulators."
No. Sentence Comment
64 In addition to the mutants G268V and ⌬Y490, we were able to facilitate processing of P-glycoproteins with mutations in the predicted transmembrane segments (TM1, G54V; TM5, G300V; TM7, A718L; and TM9, A841L), in the extracellular loops between transmembrane segments (G854V), in the cytoplasmic loops (G251V and W803A), in the nucleotide-binding domains (G427C and S434C), and in the linker region connecting the two halves of the molecule (E707A) (data not shown).
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ABCB1 p.Trp803Ala 8995353:64:319
status: NEW
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PMID: 24275649 [PubMed] Loo TW et al: "Locking intracellular helices 2 and 3 together inactivates human P-glycoprotein."
No. Sentence Comment
79 It was Clamping IH2 to IH3 Inhibits P-gp 230 JOURNAL OF BIOLOGICAL CHEMISTRY VOLUME 289ߦNUMBER 1ߦJANUARY 3, found that two mutations in IH3 (W803A and F804A) inhibited maturation of P-gp (Fig. 1, B and C) so that immature 150-kDa P-gp was the major product.
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ABCB1 p.Trp803Ala 24275649:79:155
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83 Because W803A and F804A mutations in IH3 yielded the immature 150-kDa immature P-gp as the major product, we tested whether the mutants could be rescued with cyclosporine A.
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ABCB1 p.Trp803Ala 24275649:83:8
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85 Accordingly, the A52-tagged mutants W803A and F804A were expressed in HEK 293 cells in the absence or presence of 5 òe;M cyclosporine A, and whole cell SDS extracts were subjected to immunoblot analysis. Fig. 2A shows that expression of either W803A or F804A in the presence of cyclosporine A yielded the mature 170-kDa P-gp as the major product.
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ABCB1 p.Trp803Ala 24275649:85:36
status: NEW
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ABCB1 p.Trp803Ala 24275649:85:248
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89 To determine whether the W803A and F804A mutants rescued with cyclosporine A were active, the histidine-tagged mutants W803A and F804A were expressed in HEK 293 cells in the presence of cyclosporine A, and P-gp was isolated by nickel-chelate chromatography.
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ABCB1 p.Trp803Ala 24275649:89:25
status: NEW
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ABCB1 p.Trp803Ala 24275649:89:119
status: NEW
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101 Drug rescue of processing mutants and activity of IH3 mutants W803A and F804A.
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ABCB1 p.Trp803Ala 24275649:101:62
status: NEW
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102 A52-tagged WT P-gp, mutants W803A and F804A (A), or IH3 flanking mutants (F793A, L797A, L814A, and L818A) (B) were expressed in HEK293cellsintheabsence(afa;)orpresence(af9;)of5òe;M cyclosporineA(Cyclo) for 18 h, and whole cell extracts were subjected to immunoblot analysis.
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ABCB1 p.Trp803Ala 24275649:102:28
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103 The positions of mature (170-kDa) and immature (150-kDa) forms of P-gp are shown. C, verapamil-stimulated ATPase activities of histidine-tagged wild-type P-gp and W803A and F804A mutants.
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ABCB1 p.Trp803Ala 24275649:103:163
status: NEW
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