ABCB3 p.Ala192Thr
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PMID: 9521654
[PubMed]
Kwan T et al: "Mutational analysis of the P-glycoprotein first intracellular loop and flanking transmembrane domains."
No.
Sentence
Comment
191
Group 2 comprised 19 mutants with intermediate phenotypes: Q128H, A136V, Q139H, Q139P, Q139R, E155G, E155K, S176P, K177I, E180G, G183D, D184N, A192T, F200L, F204S, R206L, L210I, T211P, and V213A; these were found throughout the mutagenized segment, with a cluster at the C-terminal portion of IC1.
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ABCB3 p.Ala192Thr 9521654:191:143
status: NEW194 Such mutants showed near wild-type transport Table 1: Summary of Mutations Identifieda TM2 IC1 TM3 EC2 TM4 Q128H R138H F159I S176P G187E R206L L210I Q128R Q139H V161E K177I A192T W208G T211P L134P Q139P H162R N179S F200L K209E V213A A136V Q139R T169I E180G F204S I214L Q145H R170L G181R I214T F147L L171P G183D S224P F148S T172P D184N E155G D174G E155K S176F a Summary of the mutations identified in the current screen together with their position within the predicted secondary structure of P-glycoprotein, with respect to the second (TM2), third (TM3), and fourth (TM4) predicted transmembrane domains together with the first intracellular (IC1) and second extracellular loop (EC2).
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ABCB3 p.Ala192Thr 9521654:194:173
status: NEW50 Mutants Q128R, Q139H, F147L, E155L, T169I, T172P, G181R, A192T, W208G, L210I, and S224P were introduced into pHILD2mdr3 by the direct replacement of an internal 1.6 kb Afl II/Sma I mdr3 cDNA subfragment (pst 170 to 1764) by the corresponding mutated mdr3 cDNA segment in pVTM3IC1.
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ABCB3 p.Ala192Thr 9521654:50:57
status: NEW197 Other mutants in this group including A192T and L210I retained robust activity against FK506 and VAL, but showed a severe reduction in mating activity.
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ABCB3 p.Ala192Thr 9521654:197:38
status: NEW223 The P. pastoris expression system was used to express and functionally characterize a representative subset of 11 loss of function mutants mapping to the various structural domains targeted for random mutagenesis: Q128R, Q139H, F147L, E155K, T169I, T172P, G181R, A192T, W208G, L210I, and S224P.
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ABCB3 p.Ala192Thr 9521654:223:263
status: NEW252 Two other mutants showed VRP and VAL-stimulated specific activities that were intermediate: T172P (53%, 26% of WT) and A192T (45%, 29% of WT).
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ABCB3 p.Ala192Thr 9521654:252:119
status: NEW256 The Km of the VRP stimulated ATPase activity was found to be in the same range for the mutants F147L, T172P, A192T, and W208G, which was between 0.6 and 1.0 mM and similar to the WT isoform.
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ABCB3 p.Ala192Thr 9521654:256:109
status: NEW270 Table 2: ATPase Activities of P-gp Mutantsa no drug, Vmax Vmax VRP stimulation KM pHILD2 0.037 0.031 0.8 ND WT 0.028 0.078 2.8 0.6 Q128R 0.022 0.034 1.6 ND Q139H 0.023 0.028 1.3 ND F147L 0.039 0.081 2.0 0.8 E155K 0.033 0.034 1.0 ND T169I 0.014 0.017 1.2 ND T172P 0.032 0.056 1.7 0.9 G181R 0.032 0.033 1.1 ND A192T 0.035 0.052 1.5 0.6 W208G 0.046 0.100 2.2 0.9 L210I 0.042 0.046 1.1 ND S224P 0.032 0.032 1.0 ND a Summary of kinetic analysis performed on a representative sample of mutants.
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ABCB3 p.Ala192Thr 9521654:270:308
status: NEW312 The most extreme examples of such mutations were Q139H, Q139R, F147L, and A192T that retained close to wild-type activity against one or more substrates but showed complete loss of function toward another one.
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ABCB3 p.Ala192Thr 9521654:312:74
status: NEW328 This group consisted of mutants in TM2 (Q128R), IC1 (Q139H, F147L, E155K, T169I, T172P, G181R), TM3 (A192T), EC2 (W208G), and TM4 (L210I, S224P).
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ABCB3 p.Ala192Thr 9521654:328:101
status: NEW