ABCMdb

ABCB3 p.Gly181Arg

None has been submitted yet.

Publications

PMID: 9521654 [PubMed] Kwan T et al: "Mutational analysis of the P-glycoprotein first intracellular loop and flanking transmembrane domains."

No. Sentence Comment

194 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). Login to comment
50 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. Login to comment
172 Certain mutations were detected more than once in our screen; these included T169I (2×), L171P (2×), T172P (4×), E180G (2×), and G181R (2×). Login to comment
188 Group 1 comprised 17 mutants, including Q128R, L134P, F147L, F148S, F159I, V161E, H162R, T169I, R170L, L171P, T172P, G181R, G187E, W208G, K209E, I214L, and S224P. Login to comment
207 This was particularly important in the case of Mdr3 mutants such as Q128R, L134P, V161E, R170L, L171P, G181R, G187E, and S224P that show complete loss of function in the three assays conducted. Login to comment
223 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. Login to comment
253 The remaining mutants (Q128R, Q139H, E155K, T169I, G181R, L210I, and S224P) had no significant level of ATP hydrolysis above background (pHILD2 negative control). Login to comment
257 Km values could not be determined for the remaining mutants (Q128R, Q139H, E155K, T169I, G181R, L210I, S224P) which displayed no significant drug-stimulated ATP hydrolysis above background. Login to comment
270 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. Login to comment
328 This group consisted of mutants in TM2 (Q128R), IC1 (Q139H, F147L, E155K, T169I, T172P, G181R), TM3 (A192T), EC2 (W208G), and TM4 (L210I, S224P). Login to comment
329 Mutants showing either complete loss of function in all three assays (e.g. Q128R, G181R) or retaining near wild-type activity for at least one of the substrates tested (e.g. Q139H, F147L) were included in this study. Login to comment