ABCC1 p.Glu1204Asp
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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."
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5
In contrast, organic anion transport by E1204L was substantially reduced, whereas transport by E1204D was comparable with wild-type MRP1, with the notable exception of GSH.
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ABCC1 p.Glu1204Asp 15208328:5:95
status: NEW118 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).
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ABCC1 p.Glu1204Asp 15208328:118:103
status: NEWX
ABCC1 p.Glu1204Asp 15208328:118:684
status: NEW124 Immunoblots showed that expression levels of the R1202G and R1202L mutants (Fig. 3B) and the E1204L and E1204D mutants (Fig. 3C) ranged from 80 to 225% of wild-type MRP1.
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ABCC1 p.Glu1204Asp 15208328:124:104
status: NEW134 To determine whether the substrate-selective loss of transport function observed in the E1204L mutant was because of the loss of the acidic character or the change in the size of the side chain, organic anion uptake by the same-charge mutant, E1204D, was also assessed.
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ABCC1 p.Glu1204Asp 15208328:134:243
status: NEW135 As shown in Fig. 4, E-H, and Table I, the E1204D mutant exhibited transport levels comparable with wild-type MRP1 for all substrates tested.
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ABCC1 p.Glu1204Asp 15208328:135:42
status: NEW137 As shown in Fig. 4I, both E1204L and E1204D exhibited a similar and substantial decrease in GSH transport levels (Ͼ75%).
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ABCC1 p.Glu1204Asp 15208328:137:37
status: NEW139 In general, the neutral mutants of Arg1202 showed only moderate and substrate-specific decreases in their transport activities. On the other hand, a neutral substitution of Glu1204 reduced or eliminated transport of all organic anions except MTX, whereas substitution with Asp had no effect with the exception that E1204D no longer transported GSH (see Table I for summary).
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ABCC1 p.Glu1204Asp 15208328:139:315
status: NEW172 E-H, uptake of 3 H-labeled organic anions by the membrane vesicles shown in Fig. 3C which were prepared from cells transfected with empty pcDNA3.1 vector (open bars), vector containing wild-type MRP1 cDNA (black bars), and the Glu1204 mutant E1204L and E1204D cDNAs (gray bars).
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ABCC1 p.Glu1204Asp 15208328:172:253
status: NEW206 Nevertheless, the substrate (LTC4)-binding site of E1204L remained intact. Furthermore, GSH transport remained very low, although other MRP1 transport activities of the same-charge E1204D mutant were comparable with wild-type MRP1.
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ABCC1 p.Glu1204Asp 15208328:206:181
status: NEW
PMID: 16815813
[PubMed]
Choudhuri S et al: "Structure, function, expression, genomic organization, and single nucleotide polymorphisms of human ABCB1 (MDR1), ABCC (MRP), and ABCG2 (BCRP) efflux transporters."
No.
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Comment
411
In contrast, replacement with same charge residue (Glu1204Asp) did not have any effect, except for GSH.
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ABCC1 p.Glu1204Asp 16815813:411:51
status: NEW