ABCMdb

ABCC1 p.Phe594Ala

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Publications

PMID: 14561746 [PubMed] Campbell JD et al: "Molecular modeling correctly predicts the functional importance of Phe594 in transmembrane helix 11 of the multidrug resistance protein, MRP1 (ABCC1)."

No. Sentence Comment

6 Substitution of Phe594 with Ala substantially reduced or eliminated the transport of five organic anion substrates by MRP1 and abrogated the binding of leukotriene C4. Login to comment
51 To test this hypothesis, we used site-directed mutagenesis to replace MRP1-Phe594 with Ala, Trp, and Tyr and examined the transport and organic anion binding properties of these mutants. Login to comment
69 Phe594 substitutions were generated in the pBluescriptSK(ϩ) plasmid above according to the manufacturer`s instructions with the following mutagenic primers (substituted nucleotides are underlined): F594A, 5Ј-G TTC AAC ATC CTC CGG GCT CCC CTG AAC ATT CTC C-3Ј; F594W, 5Ј-C TTG TTC AAC ATC CTC CGC TGG CCC CTG AAC ATT CTC CCC-3Ј; and F594Y, 5Ј-G TTC AAC ATC CTC CGC TAT CCC CTG AAC ATT CTC C-3Ј. Login to comment
99 LTC4 Transport and Photo-labeling Is Eliminated by Ala Substitution of Phe594 -As shown in Fig. 2A, all three mutants generated (F594A, F594W, and F594Y) were expressed at levels 60-100% of those of wild-type MRP1 in transfected HEK cells. Login to comment
102 After correcting for differences in MRP1 protein expression levels, ATP-dependent LTC4 uptake by the F594A mutant was reduced by more than 90%, whereas uptake by the F594W and F594Y mutants was comparable with that by wild-type MRP1. Login to comment
103 To further investigate the loss of LTC4 transport by the F594A mutant, protein-labeling experiments were carried out with this intrinsically photoactivatable arachidonic acid derivative. Login to comment
111 A, representative immunoblot of membrane vesicles prepared from HEK293T cells transfected with empty vector (pcDNA3.1(-)), wild-type (WT-MRP1), and mutant (F594A, F594W, and F594Y) MRP1 cDNAs. Login to comment
121 In contrast, no such band is detectable in photolabeled vesicles from cells expressing comparable levels of the F594A mutant. Login to comment
122 This indicates that this non-conservative substitution of Phe594 abrogates photolabeling by LTC4 and, hence, binding of this substrate to MRP1, a finding that is consistent with the complete loss of LTC4 transport activity by the F594A mutant. Login to comment
162 Thus, although the aromatic properties of the residue at position 594 are critical for retaining overall activity (i.e. F594 (wild-type), F594W, and F594Y are active but F594A is not), the addition of hydrogen bonding capacity to the amino acid side chain (as in F594W and F594Y) also influences substrate specificity, as shown previously for the polar aromatic residues at positions 553, 1198, 1243, and 1246. Login to comment

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

136 Nonconservative mutation of Phe594 to Ala resulted in decreased transport of all substrates tested and loss of photolabeling with LTC4. Login to comment
138 Like the F594A mutation, nonconservative substitution of the two adjacent residues Arg593 and Pro595 also decreased transport of all organic anion substrates tested (35, 49). Login to comment

PMID: 16387301 [PubMed] Deeley RG et al: "Substrate recognition and transport by multidrug resistance protein 1 (ABCC1)."

No. Sentence Comment

147 On the other hand, while alanine substitution of Phe594 eliminates LTC4 binding and overall transport activity, conservative mutations have differential effects on substrate specificity suggesting that this residue may interact directly with substrate [61]. Login to comment

PMID: 16442101 [PubMed] Frelet A et al: "Insight in eukaryotic ABC transporter function by mutation analysis."

No. Sentence Comment

465 F594A or substitution in P595 resulted in a global loss of organic anion transport and LTC4 binding [229,232]. Login to comment

PMID: 16816140 [PubMed] Deeley RG et al: "Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins."

No. Sentence Comment

910 Indeed, mutation of Phe594 to Ala drastically reduced transport of four different substrates tested and eliminated photolabeling by LTC4 (52). Login to comment
909 Indeed, mutation of Phe594 to Ala drastically reduced transport of four different substrates tested and eliminated photolabeling by LTC4 (52). Login to comment
911 Indeed, mutation of Phe594 to Ala drastically reduced transport of four different substrates tested and eliminated photolabeling by LTC4 (52). Login to comment

PMID: 16820223 [PubMed] Cole SP et al: "Transport of glutathione and glutathione conjugates by MRP1."

No. Sentence Comment

86 Accordingly, it was correctly predicted that an Ala substitution of Phe594 would adversely affect MRP1 function [38]. 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