ABCC1 p.Asn597Ala

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PMID: 15260484 [PubMed] Zhang DW et al: "Transmembrane helix 11 of multidrug resistance protein 1 (MRP1/ABCC1): identification of polar amino acids important for substrate specificity and binding of ATP at nucleotide binding domain 1."
No. Sentence Comment
7 N597A increased and decreased resistance to vincristine and VP-16, respectively, while S605A decreased resistance to vincristine, VP-16 and doxorubicin.
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ABCC1 p.Asn597Ala 15260484:7:0
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60 Mutations S585A, N590A, N590Q, N590D, N597A, and S604A were generated using the QuikchangeSite-Directed Mutagenesis kit (STRATAGENE, La Jolla, CA).
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ABCC1 p.Asn597Ala 15260484:60:38
status: NEW
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68 CGG TTT CCC-3'), N590D (5'-CT TTG GCC TTG TTC GAT ATC CTC CGG TTT CCC-3'), N597A (5'-CTC CGG TTT CCC CTG GCC ATT CTC CCC ATG GT-3'), and S604A (5'-CTC CCC ATG GTC ATC GCC AGC ATC GTG CAG GC-3') After confirming all mutations by DNA Thermo Sequenase Cy5.5 and Cy5.0 dye terminator cycle sequencing (Amersham Biosciences) according to the manufacturer`s instructions, DNA fragments containing the desired mutations were transferred into pCEBV7-MRP1.
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ABCC1 p.Asn597Ala 15260484:68:75
status: NEW
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151 The levels of LTC4 uptake by vesicles prepared from HEK transfectants expressing either wild-type MRP1 or mutations Q580A, T581A, S585A, N597A, S604A, and S605A were proportional to the relative expression levels of the wild-type and mutant proteins.
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ABCC1 p.Asn597Ala 15260484:151:137
status: NEW
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154 Mutations Q580A, T581A, S585A, N597A, and S605A had no detectable effect on transport.
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ABCC1 p.Asn597Ala 15260484:154:31
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204 In contrast, conversion of Asn597 to Ala resulted in a mutant protein with enhanced resistance to vincristine (3-4-fold) but an approximately 3-fold decrease in the ability to confer resistance to VP-16 without any significant effect on doxorubicin resistance.
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ABCC1 p.Asn597Ala 15260484:204:27
status: NEW
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216 In contrast, mutations N597A and S605A influenced only the drug resistance profile of MRP1, and mutation S604A affected the transport of only E217 G.
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ABCC1 p.Asn597Ala 15260484:216:23
status: NEW
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221 Other mutations, including N597A and S605A, which influenced MRP1-mediated drug resistance, had no effect, suggesting that they modify interactions between MRP1 and the drug rather than altering the ability to bind and transport GSH.
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ABCC1 p.Asn597Ala 15260484:221:27
status: NEW
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269 Consistently, we found that replacement of Asn597 with Ala increased resistance to larger drugs such as vincristine and decreased resistance to smaller substrates such as VP-16.
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ABCC1 p.Asn597Ala 15260484:269:43
status: NEW
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273 In addition, mutations N597A and S605A affected only the drug-resistance profile of MRP1.
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ABCC1 p.Asn597Ala 15260484:273:23
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PMID: 17295059 [PubMed] Chang XB et al: "A molecular understanding of ATP-dependent solute transport by multidrug resistance-associated protein MRP1."
No. Sentence Comment
112 Many mutations in TM11, such as N590A, F594A, N597A, S604A and S605A, also modulate the drug resistance profile of MRP1 [79, 80].
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ABCC1 p.Asn597Ala 17295059:112:46
status: NEW
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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.
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ABCC1 p.Asn597Ala 19949927:104:173
status: NEW
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