ABCMdb

ABCC1 p.Trp1198Tyr

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Publications

PMID: 12388549 [PubMed] Koike K et al: "Multiple membrane-associated tryptophan residues contribute to the transport activity and substrate specificity of the human multidrug resistance protein, MRP1."

No. Sentence Comment

48 Tryptophan substitutions were generated in the pGEM-3Z and pBluescriptSK(ϩ) plasmids above according to the manufacturer`s instructions with the following mutagenic primers (substituted nucleotides are underlined): MSD1 Trp mutants W40A (5Ј-G GTC CTC GTG GCC GTG CCT TG-3Ј, W47A (5Ј-GT TTT TAC CTC GCC GCC TGT TTC CCC-3Ј), W82A (5Ј-C TTG GGA TTT TTG CTG GCG ATC GTC TGC TGG GC-3Ј), W86A (5Ј-G CTG TGG ATC GTC TGC GCT GCA GAC CTC TTC TAC TC-3Ј), W94A (5Ј-C CTC TTC TAC TCT TTC GCG GAA AGA AGT CGG GGC-3Ј), W142A (5Ј-GGG ATC ATG CTC ACT TTC GCA CTG GTA GCC CTA ATG TG-3Ј), W142F (5Ј-G CTC ACT TTT TTC CTG GTA GCC C-3Ј); MSD2 Trp mutants W361A (5Ј-C ACG AAG GCC CCA GAT GCG CAG GGC TAC TTC TAC-3Ј), W445A (5Ј-G TAC ATT AAC ATG ATC GCG TCA GCC CCC CTG CAA G-3Ј), W445F (5Ј-CG TAC ATT AAC ATG ATC TTC TCA GCC CCC CTG CAA GTC-3Ј), W445Y (5Ј-CC ACG TAC ATT AAC ATG ATC TAC TCA GCG CCC CTG CAA GTC-3Ј), W459A (5Ј-GCT CTC TAC CTC CTG GCG CTG AAT CTG GGC CC-3Ј), W553A (5Ј-G GGC ACC TTC ACC GCG GTC TGC ACG CCC-3Ј), W553F (5Ј-G GGC ACC TTC ACC TTC GTC TGC ACG CCC-3Ј), W553Y (5Ј-GCC CTG GGC ACC TTC ACA TAT GTC TGC ACG CCC-3Ј; and MSD3 Trp mutants W1198A (5Ј-C GTG GCC AAC AGG GCG CTG GCC GTG CGG C-3Ј), W1198F (5Ј-GTG GCC AAC AGG TTC CTG GCC GTG CGG C-3Ј), W1198Y (5Ј-GTG GCC AAC AGG TAC CTG GCC GTG CGG C-3Ј). Login to comment
145 Thus, the LTC4, GSH, and E13SO4 transport activities of the W1198F mutant were similar to those of wild-type MRP1, whereas transport of these substrates by the W1198Y mutant exceeded that of wild-type MRP1 (Fig. 6, B, D, and E). Login to comment
146 Transport of E217betaG and MTX by the W1198F and W1198Y mutants was ϳ50-75% that of wild-type MRP1 when corrected for relative MRP1 expression levels (Fig. 6, C and F). Login to comment
147 For all substrates, transport activity was restored more effectively when Trp1198 was mutated to Tyr compared with Phe, suggesting that, as observed for the Trp445 mutants, both the aromatic and polar properties of the Trp residue at position 1198 contribute to MRP1 transport activity. Login to comment
189 Ala substitution of Trp1198 in MSD3 also resulted in a broad and profound decrease in MRP1 transport activity except for FIG. 6. ATP-dependent organic anion transport activity of wild-type and mutant MRP1 containing conservative Phe and Tyr substitutions of Trp1198 in TM16 of MSD3. A, immunoblot of membrane vesicles prepared from HEK293T cells transfected with empty vector (pcDNA3.1(-)), wild-type (WT-MRP1), and mutant (W445A, W445F, and W445Y; W553A, W553F and W553Y; W1198A, W1198F, and W1198Y) MRP1 cDNAs. MRP1 proteins were detected with monoclonal antibody QCRL-1, and relative levels of expression shown under the blot were estimated by densitometry. Login to comment
190 B-F, relative levels of 3 H-labeled organic anion uptake by the membrane vesicles shown in A enriched for wild-type MRP1 (solid bar), Trp 3 Phe-substituted MRP1 mutants (W445F, W553F, and W1198F; hatched bars), and Trp 3 Tyr-substituted MRP1 mutants (W445Y, W553Y, and W1198Y; open bars) were determined as described under "Experimental Procedures." Login to comment

PMID: 20004175 [PubMed] de Foresta B et al: "Interaction with membrane mimics of transmembrane fragments 16 and 17 from the human multidrug resistance ABC transporter 1 (hMRP1/ABCC1) and two of their tryptophan variants."

No. Sentence Comment

348 For TM16, the variant results from the following two point mutations: W1198Y and F1113W. Login to comment