ABCC1 p.Tyr568Ala
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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
34
In TM10, Thr550 , Thr552 , Thr556 , Thr564 , and Thr570 were individually mutated to Ala, and Tyr568 was mutated to Ala, Ser, Phe, and Trp.
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ABCC1 p.Tyr568Ala 16415113:34:94
status: NEW48 Mutations T550A, T552A, T556A, Y568A, Y568S, Y568F, Y568W, T570A, and N1208A were generated using the Quikchange Site-Directed Mutagenesis kit (Stratagene, La Jolla, CA).
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ABCC1 p.Tyr568Ala 16415113:48:31
status: NEW50 Oligonucleotides bearing mismatched bases at the residues to be mutated (underlined) were synthesized by ACGT Corp. with the following sequences: T550A, 5Ј-GTCAGCCGTGGG- CGCCTTCACCTGGGT-3Ј; T552A, 5Ј-CGTGGGCACCTTCGCCTGGGTC- TGCAC-3Ј; T556A, 5Ј-CACCTGGGTCTGCGCGCCCTTTCTGGT-3Ј; Y568A, 5Ј-TGCACATTTGCCGTCGCCGTGACCATTGACGA-3Ј; Y568S, 5Ј-TGCACATTTGCCGTCTCCGTGACCATTGACGA-3Ј; Y568F, 5Ј-TGC- ACATTTGCCGTCTTCGTGACCATTGACGA-3Ј; Y568W, 5Ј-TGCACAT- TTGCCGTCTGGGTGACCATTGACGA-3Ј; T570A, (5Ј-TGCCGTCTACG- TGGCCATTGACGAGAACAAC-3Ј; and N1208A, 5Ј-GCCGTGCGGCTG- GAGTGTGTGGGCGCC-3Ј.
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ABCC1 p.Tyr568Ala 16415113:50:312
status: NEW120 ATP-dependent transport of [3 H]E217betaG was also examined (Fig. 3, D to F), only replacement of Tyr568 with Ala decreased the transport efficiency by approximately 60%, indicating that the polar and/or the bulky aromatic side chain of the residue at position 568 is important for the ability of MRP1 to transport E217betaG.
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ABCC1 p.Tyr568Ala 16415113:120:98
status: NEW122 Because replacement of Tyr568 by Ala selectively decreased transport of E217betaG, this residue was also mutated to Ser, Phe, and Trp.
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ABCC1 p.Tyr568Ala 16415113:122:23
status: NEW126 Like mutation Y568A, substitution of Tyr568 with Ser did not affect the transport of LTC4 but decreased E217betaG transport.
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ABCC1 p.Tyr568Ala 16415113:126:14
status: NEW129 Kinetic Parameters of [3 H]LTC4 and [3 H]E217betaG Transport by Wild-Type and Y568A Mutant MRP1.
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ABCC1 p.Tyr568Ala 16415113:129:78
status: NEW130 To more precisely determine the influence of mutation Y568A on the ability of MRP1 to transport E217betaG, we compared kinetic parameters for the wild-type and mutant proteins (Fig. 5).
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ABCC1 p.Tyr568Ala 16415113:130:54
status: NEW131 For wild-type MRP1 and Y568A, the Km and normalized Vmax values for LTC4 uptake were essentially identical.
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ABCC1 p.Tyr568Ala 16415113:131:23
status: NEW132 Linear regression using a Hanes-Woolf transformation yielded values of 115 nM and 143 nM, and 76.8 pmol/mg/min and 64 pmol/mg/min, for the Km and Vmax values of wild-type and Y568A proteins, respectively (Fig. 5, B and C).
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ABCC1 p.Tyr568Ala 16415113:132:175
status: NEW151 We have shown that mutations T550A and T556A both affect the ability of MRP1 to confer drug resistance, whereas mutation Y568A only influenced the transport of E217betaG.
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ABCC1 p.Tyr568Ala 16415113:151:121
status: NEW233 However, kinetic analysis showed that the nonconservative mutation Y568A increased the apparent Km for E217betaG approximately 5-fold, without altering Vmax.
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ABCC1 p.Tyr568Ala 16415113:233:67
status: NEW
PMID: 21701864
[PubMed]
de Foresta B et al: "Transverse and tangential orientation of predicted transmembrane fragments 4 and 10 from the human multidrug resistance protein (hMRP1/ABCC1) in membrane mimics."
No.
Sentence
Comment
61
Mutations resulting in the replacement of two of its threonine residues (T550A and T556A) modulated the drug-resistance profile of hMRP1 and a mutation affecting the tyrosine residue (Y568A) reduced the affinity of hMRP1 for E217bG (Zhang et al. 2006).
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ABCC1 p.Tyr568Ala 21701864:61:184
status: NEW