ABCB1 p.Gln946Ala

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PMID: 10585407 [PubMed] Loo TW et al: "Identification of residues in the drug-binding domain of human P-glycoprotein. Analysis of transmembrane segment 11 by cysteine-scanning mutagenesis and inhibition by dibromobimane."
No. Sentence Comment
79 Wild-type P-gp had an apparent affinity of 24 ␮M verapamil, while mutants F942A, T945A, Q946A, A947L, and Y953A had decreased apparent affinities of 93, 100, 165, 156, and 110 ␮M, respectively.
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ABCB1 p.Gln946Ala 10585407:79:95
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84 Moderate decreases in activity (40-50%) were observed for mutants G939V, Q946A, A947L, Y953A, and F957A.
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ABCB1 p.Gln946Ala 10585407:84:73
status: NEW
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100 There were, however, significant decreases in the activity for mutants Q946A (18%), F942A (24%), and F957A (32%).
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ABCB1 p.Gln946Ala 10585407:100:71
status: NEW
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128 TABLE I Drug-stimulated ATPase activity Mutant Drug Verapamil Vinblastine Colchicine Vmax Km Vmax Km Vmax Km % of WTa ␮M % of WT ␮M % of WT mM WT 100 24 100 5.4 100 0.62 I937S 94 22 93 6.1 100 0.69 F938A 106 32 96 5.1 96 0.68 G939V 62 8 45 4.0 165 0.26 I940S 93 32 93 5.6 93 0.65 T941A 100 25 104 5.5 100 0.66 F942A 88 93 30 5.1 24 0.80 S943A 92 26 100 5.2 85 0.62 F944A 93 14 105 5.3 101 0.64 T945A 140 100 165 8.3 56 0.65 Q946A 101 165 57 8.5 18 0.64 A947L 105 156 60 13.0 51 1.87 M948A 103 23 101 5.9 103 0.62 M949A 82 40 96 5.5 61 0.60 Y950A 109 37 119 5.1 99 0.62 F951A 94 31 99 5.2 101 0.64 S952A 108 36 123 5.1 91 0.69 Y953A 205 110 59 8.5 131 0.67 A954L 108 44 13 NDb 8 ND G955V 143 10 104 3.5 220 0.47 C956A 97 24 95 5.3 145 0.63 F957A 126 21 47 4.8 32 1.0 a WT, wild type. b ND, not determined due to low activity.
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ABCB1 p.Gln946Ala 10585407:128:438
status: NEW
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147 DISCUSSION Mutants G939V, F942A, T945A, Q946A, A947L, and Y953A in TM11 had altered apparent affinities for verapamil, vinblastine, or colchicine.
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ABCB1 p.Gln946Ala 10585407:147:40
status: NEW
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PMID: 18596043 [PubMed] Loo TW et al: "Arginines in the first transmembrane segment promote maturation of a P-glycoprotein processing mutant by hydrogen bond interactions with tyrosines in transmembrane segment 11."
No. Sentence Comment
219 The presence of mutations Q946A, M948A, M949A, F951A, or S952A did not appear to affect the maturation of the M68R/ G251V mutant (Fig. 8A, lanes 2-5, 7, and 8).
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ABCB1 p.Gln946Ala 18596043:219:26
status: NEW
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