ABCMdb

ABCC3 p.Gln1235Ala

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Publications

PMID: 12924948 [PubMed] Zhang DW et al: "Characterization of the role of polar amino acid residues within predicted transmembrane helix 17 in determining the substrate specificity of multidrug resistance protein 3."

No. Sentence Comment

7 Mutation Q1235A also reduced resistance to VP-16 and transport of E217βG but increased taurocholate transport without affecting transport of methotrexate. Login to comment
75 They are as follows: S1229A (5'-GGG CTG GTG GGG CTA GCT GTG TCC TAC TCC-3'), S1231A (5'-GC CTT TCT GTG GCC TAC TCC CTG CAG GTG ACA-3'), Y1232F (5'-T TCT GTG TCC TTC TCC TTA CAG GTG ACA TTT G-3'), S1233A (5'-CT GTG TCC TAC GCC CTG CAG GTG ACA TTT G-3'), Q1235A (5'-G TCC TAC TCC TTG GCG GTG ACA TTT GCT C-3'), T1237A (5'-CC TTG CAG GTG GCA TTC GCT CTG AAC TGG-3'), T1237S (5'-CC TTG CAG GTG TCC TTC GCT CTG AAC TGG-3'), T1237G (5'-CC TTG CAG GTG GGA TTC GCT CTG AAC TGG-3'), T1237L (5'-CC TTG CAG GTG CTA TTC GCT CTG AAC TGG-3'), and N1241A (5'-GTG ACA TTT GCG CTA GCC TGG ATG ATA C-3'). Login to comment
138 Replacement of Ser1229 with Ala had no significant effect on MRP3-mediated E217βG uptake, whereas mutations S1231A, Y1232F, S1233A, Q1235A, and N1241A all decreased the transport activity. Login to comment
141 Replacement of Gln1235 by Ala had no FIGURE 1: Resistance of stably transfected HEK293 cells to cisplatin (B), doxorubicin (C), vincristine (D), and VP-16 (E). Login to comment
151 In contrast, mutations Q1235A and T1237A increased the ability of MRP3 to transport the bile salt approximately 1.5-and 3-fold, respectively. Login to comment
155 Like mutation T1237A, replacement of Gln1235 with Ala also increased taurocholate uptake. Login to comment
160 The results suggest that mutations Q1235A and T1237A affect a step in the transport process after initial binding of this substrate. Login to comment
161 The effects of mutations Q1235A and T1237A on kinetic parameters of E217βG transport were also examined (Figure 7B, Table 1). Login to comment
162 Mutation Q1235A had no significant effect on the Km values (29 and 32 µM for wild-type MRP3 and mutant MRP1Q1235A , respectively) but decreased the Vmax FIGURE 2: Transport of taurocholate by MRP3. Panel A: Time course of ATP-dependent [3H]taurocholate uptake by membrane vesicles prepared from HEK293 stable transfectant expressing wild-type MRP3. Membrane vesicles were incubated at 37 °C with 4 µM [3H]taurocholate in transport buffer for the time indicated, as described. Login to comment
179 Thus, similar to the results obtained with taurocholate as a substrate, mutation Q1235A appeared not to influence the initial binding of the conjugated estrogen to the protein. Login to comment
186 However, mutation of five hydrophilic amino acid residues (S1231A, Y1232F, S1233A, Q1235A, and N1241A) caused approximately a 2-3-fold reduction of resistance to VP-16. Login to comment
188 Thus, on the basis of the substrates tested in this study, mutations S1229A, S1231A, Q1235A, and N1241A affected substrate specificity of MRP3, whereas mutations Y1232F, S1233A, and T1237A influenced the overall activity of the protein. Login to comment
277 Consistent with this possibility, mutation Q1235A increased and decreased the Vmax for transport of taurocholate and E217βG, respectively, without affecting the Km for either substrate. Login to comment
285 Mutation Q1235A caused a decrease in VP-16 resistance and E217βG transport, consistent with the involvement of hydrogen bonding in the interaction with these substrates, but the mutation increased taurocholate transport. Login to comment