ABCMdb

ABCC1 p.Thr556Ala

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Publications

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

6 Although mutation of Asn1208 was without effect, two of six mutations in TM10, T550A and T556A, modulated the drug resistance profile of MRP1 without affecting transport of leukotriene C4, 17beta-estradiol 17-(beta-D-glucuronide) (E217betaG), and glutathione. Login to comment
7 Mutation T550A increased vincristine resistance but decreased doxorubicin resistance, whereas mutation T556A decreased resistance to etoposide (VP-16) and doxorubicin. Login to comment
48 Mutations T550A, T552A, T556A, Y568A, Y568S, Y568F, Y568W, T570A, and N1208A were generated using the Quikchange Site-Directed Mutagenesis kit (Stratagene, La Jolla, CA). Login to comment
50 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. Login to comment
148 In contrast, mutation T556A reduced the resistance to both VP-16 and doxorubicin approximately 2-fold without affecting vincristine resistance. Login to comment
151 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. Login to comment

PMID: 17295059 [PubMed] Chang XB et al: "A molecular understanding of ATP-dependent solute transport by multidrug resistance-associated protein MRP1."

No. Sentence Comment

111 The P557A mutation in TM10 also exhibited significantly reduced transport of five organic anion substrates [75], whereas the other two mutations in TM10, T550A and T556A, modulate the drug resistance profile of MRP1 [78]. Login to comment

PMID: 19949927 [PubMed] Chang XB et al: "Molecular mechanism of ATP-dependent solute transport by multidrug resistance-associated protein 1."

No. Sentence Comment

104 Mutations of C43S in TM1 (112); P343A, K332L and K332D in TM6 (113, 114); W445A and P448A in TM8 (113, 115); T550A, T556A and P557A in TM10 (113, 116); N590A, F594A, P595A, N597A, S604A and S605A in TM11 (113, 117, 118); E1089Q, E1089A, E1089L, E1089N, K1092, S1097 and N1100 in TM14 (119, 120); R1197K in TM16 (121); Y1236F, T1241A, T1242A, T1242C, T1242S, T1242L, Y1243F, N1245A, W1246C, W1246A, W1246F, W1246Y or R1249K in TM17 (121-124) significantly affect MRP1 function. Login to comment

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). 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

36 For example, mutations of two threonine (T550A and T556A), a tryptophan (W553A), and a proline (P557A) in TM10 modify the drug-resistance profile of the protein or decrease the transport of various organic substrates [32-35]. Login to comment