ABCMdb

ABCB4 p.Asn1042Asp

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Publications

PMID: 7568044 [PubMed] Volkman SK et al: "Functional complementation of the ste6 gene of Saccharomyces cerevisiae with the pfmdr1 gene of Plasmodium falciparum."

No. Sentence Comment

38 Shuttle plasmids constructed with the pYES-2 vector (Invitrogen) contained either the wild-typepfindrl gene (pYpfmdrl) or a mutantpfindrl gene with a serine to cysteine change at position 1034 and an asparagine to aspartic acid change at position 1042 (pYpfmdrlCD) (2). Login to comment

PMID: 11512154 [PubMed] Peel SA et al: "The ABC transporter genes of Plasmodium falciparum and drug resistance."

No. Sentence Comment

52 Expression of the 7G8 chloroquine-resistance mutations, Cys-1034 and Asp-1042, implicated in chloroquine resistance, resulted in loss-of-function mutants (i.e. abolished the mating phenotype), suggesting that these genetic polymorphisms alter transport function.82 It should be noted that a similar study analyzing quinoline antimalarials in a ste6 mutant strain was recently withdrawn from publication due to contamination of transformants with wild-type ste6 sequences.86,87 The advance of stable transgene transfection of in-vitro cultured P. falciparum has permitted in vivo analysis of the functional significance of Pgh1.88 Elegant experiments by Reed et al.89 have offered the first definitive evidence that polymorphisms in pfmdr 1 can confer resistance to mefloquine, halofantrine, and quinine.These authors also demonstrated that polymorphisms of pfmdr 1 can modulate levels of chloroquine resistance in a strain-specific manner, as well as modulate sensitivity to the structurally unrelated antimalarial artemisinin Three of the 7G8 intra-alleles Ser 1034Cys , Asn 1042Asp , Asp 1246Tyr implicated in chloroquine resistance were examined by allelic exchange of the endogenous pfmdr 1 locus. Login to comment

PMID: 8790436 [PubMed] Ruetz S et al: "The pfmdr1 gene of Plasmodium falciparum confers cellular resistance to antimalarial drugs in yeast cells."

No. Sentence Comment

88 The expression of the wild-type P. falciparum Pgh-1 protein (A) and mutant variants bearing single S1034C (B) or N1042D (C) mutations or both (D) in permeabilized yeast S. cerevisiae spheroplasts is shown by immunofluorescence using a specific antiserum (rabbit anti-Pgh-1) at a 1:100 dilution, followed by an fluorescein isothiocyanate-coupled goat anti-rabbit antibody at a dilution of 1:800. Login to comment
94 Time-dependent cell growth in absence (solid symbols) or presence (open symbols) of MFQ at 150 ,ug/ml was established for JPY201 transformants expressing wild-type Pgh-1, wild-type Mdr3 (Mdr3S), or Pgh-1 variants bearing single S1034C (M1034) or single N1042D (M1042) mutations or both mutations (S1034C/N1042D; DM) in predicted TM11 or a mutant variant of Mdr3 (S939F; Mdr3F). Login to comment
97 JPY201 cells expressing wild-type Pgh-1, wild-type Mdr3 (Mdr3S), or mutant Pgh-1 variants bearing single S1034C (M1034), single N1042D M1042) mutations, or both mutations (S1034C/N1042D; DM) were evaluated for growth in increasing concentrations of MFQ. Login to comment
133 JPY201 cells expressing either wild-type Pgh-1 or a double mutant Pgh-1 variant (S1034C/ N1042D; DM) were incubated with QA. Login to comment

PMID: 7511206 [PubMed] van Es HH et al: "Expression of the plasmodial pfmdr1 gene in mammalian cells is associated with increased susceptibility to chloroquine."

No. Sentence Comment

289 We expressed one of these pfmdrl alleles, S1034C/N1042D, in CHO cells and did not see the change in CQ sensitivity and accumulation as observed with wild-type Pghl, the form of Pghl commonly expressed in CQS parasites. Login to comment
303 In the absence of other plasmodial proteins, we have shown that at least one CQR-associated allele (S1034C/N1042D) abolishes the Pghl-mediated increase in CQ sensitivity and uptake into CHO cells. Login to comment