ABCMdb

ABCC1 p.Arg1197Glu

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Publications

PMID: 15208328 [PubMed] Situ D et al: "Mutational analysis of ionizable residues proximal to the cytoplasmic interface of membrane spanning domain 3 of the multidrug resistance protein, MRP1 (ABCC1): glutamate 1204 is important for both the expression and catalytic activity of the transporter."

No. Sentence Comment

107 The relative mean expression levels of the R1197E and R1249D mutants from 2 to 3 independent transfections were comparable with wild-type MRP1 (110 and 70%, respectively). Login to comment
113 Membrane vesicles prepared from HEK293T cells transfected with empty vector [pcDNA3.1] and vector containing the wild-type (WT-MRP1) and mutant (R1197E, R1202D, E1204K, and R1249D) cDNAs were immunoblotted with mAb QCRL-1. Shown is a representative immunoblot of membrane vesicles (1 and 2 ␮g of protein) from a single transfection. Login to comment
118 Immunoblots of membrane vesicle proteins prepared from cells expressing the Glu1204 mutants E1204L and E1204D were carried out as described in A. TABLE I Summary of organic anion transport activity of MRP1 mutants with substitutions of ionizable amino acids in and proximal to TM13 to TM17 of MSD3 Mutation % Wild-type MRP1 transport activitya E217betaG LTC4 E1SO4 MTX GSH TM13 R1046D 115 70 80 120 NDb TM14 D1084R Ͻ10 Ͻ10 15 25 Ͻ10 D1084E 80 20 65 90 20 TM15 R1131E 70 50 80 60 ND TM16 R1197E Ͻ10 Ͻ10 Ͻ15 Ͻ10 ND R1197K 20 Ͻ25 Ͻ20 Ͻ10 ND R1202G 115 115 75 70 ND R1202L 115 120 50 110 ND E1204L Ͻ10 50 10 110 Ͻ25 E1204D 100 115 100 115 Ͻ25 TM17 R1249D Ͻ10 Ͻ15 Ͻ10 Ͻ10 ND R1249K Ͻ10 10 Ͻ15 Ͻ10 ND a The values shown are means of duplicate or triplicate determinations and are derived from Fig. 2, 4, and 5 (see figure legends for details). Login to comment
141 Transport Activities of TM16/17 Arg1197 and Arg1249 Mutants-Unlike the R1202D and E1204K mutants, oppositely charged substitutions of Arg1197 (R1197E) and Arg1249 (R1249D) did not adversely affect expression of MRP1 (Fig. 3A). Login to comment
143 Thus, levels of E217betaG uptake by both mutants were Ͻ10% of wild-type MRP1 levels (Fig. 5A), whereas LTC4 uptake by the R1197E and R1249D mutants was Ͻ15% of wild-type MRP1 (Fig. 5B). Login to comment
144 Uptake of E1SO4 by the R1197E mutant was Ͻ15% of wild-type MRP1, whereas uptake of this sulfated estrogen by the R1249D mutant was reduced by Ͼ90% (Fig. 5C). Login to comment
145 Finally, the R1197E and R1249D mutants showed MTX transport activity that was not significantly different from the empty vector control (Fig. 5D). Login to comment
177 Levels of 3 H-labeled organic anion uptake by membrane vesicles were prepared from cells expressing wild-type MRP1 (black bars), mutants R1197E, R1197K, R1249D, and R1249K (gray bars), and empty pcDNA3.1 vector control vesicles (open bars). Login to comment

PMID: 16415113 [PubMed] Zhang DW et al: "Mutational analysis of polar amino acid residues within predicted transmembrane helices 10 and 16 of multidrug resistance protein 1 (ABCC1): effect on substrate specificity."

No. Sentence Comment

164 Conversely, replacement of Glu1204 with Leu or Arg1197 with Glu or Lys affected either substrate specificity or overall transport activity of MRP1 (Situ et al., 2004). Login to comment

PMID: 24157718 [PubMed] Abel S et al: "Bindings of hMRP1 transmembrane peptides with dodecylphosphocholine and dodecyl-beta-d-maltoside micelles: a molecular dynamics simulation study."

No. Sentence Comment

39 Indeed, mutations of the ionizable residues (for example, R1197E, R1202(G,L) and E1204L) have impact on protein expression, substrate binding and/or transport [37], whereas the mutation of a single tryptophan W1246A in TM17 affects the estradiol 17-b2;-D-glucuronide transport [36]. Login to comment