ABCMdb

ABCC1 p.Ser604Ala

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Publications

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

8 The third, S604A, selectively increased 17 -estradiol 17-( -D-glucuronide) (E217 G) transport. Login to comment
47 Ser604 was converted to Ala and Thr, and Asn590 was mutated to Ala, Gln, and Asp. Login to comment
60 Mutations S585A, N590A, N590Q, N590D, N597A, and S604A were generated using the QuikchangeSite-Directed Mutagenesis kit (STRATAGENE, La Jolla, CA). Login to comment
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. Login to comment
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. Login to comment
155 However, substitution of Ser604 with Ala (S604A) increased the transport efficiency by approximately 2-fold. Login to comment
157 Thus, mutation S604A altered only the ability of MRP1 to transport the glucuronidated estrogen, whereas mutation N590A influenced the transport of both LTC4 and E217 G. Login to comment
168 To examine the influence of the N590A and S604A mutations more quantitatively, we compared their effect on the kinetic parameters of transport of both substrates (Figure 5). Login to comment
169 Mutation S604A had no effect on either the apparent Km or Vmax values for LTC4 uptake (Km 150 and 145 nM, and Vmax 89 and 84 pmol/ mg/min for wild-type MRP1 and mutation S604A, respectively) (Figure 5B and Table 1). Login to comment
172 For E217 G transport, the Vmax value for mutation S604A was increased by 20-25% relative to wild-type MRP1 (197 pmol/mg/min for wild-type MRP1 vs 241 pmol/mg/min for the mutation), while the apparent Km was decreased ~2.5-fold (1.7 and 0.7 µM for wild-type MRP1 and mutation S604A, respectively) (Figure 5C and Table 1). Login to comment
174 Thus, as observed with LTC4 as a substrate, mutation N590A decreased the Vmax/Km ratio for E217 G approximately 3-fold, whereas the S604A mutation increased the Vmax/Km ratio for this substrate approximately 3-fold. Login to comment
175 These changes in transport efficiency were mediated predominantly by a decrease in apparent affinity for both LTC4 and E217 G as a result of the S604A mutation, while the N590A mutation increased the apparent Km and decreased the Vmax for E217 G. Login to comment
203 Mutations Q580A, T581A, S585A, S604A, and S604T had no significant effect on the ability of MRP1 to confer resistance to any drug tested. Login to comment
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. Login to comment
270 In addition, although mutation S604T had no effect on any of the MRP1 functions tested, converting Ser604 to Ala decreased the apparent Km values and increased Vmax for E217 G uptake. 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

112 Many mutations in TM11, such as N590A, F594A, N597A, S604A and S605A, also modulate the drug resistance profile of MRP1 [79, 80]. 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