ABCMdb

PMID: 21628496

Li L, Sham YY, Bikadi Z, Elmquist WF
pH-Dependent transport of pemetrexed by breast cancer resistance protein.
Drug Metab Dispos. 2011 Sep;39(9):1478-85. Epub 2011 May 31., [PubMed]

Sentences

No. Mutations Sentence Comment

43 ABCG2 p.Arg482Thr ABCG2 p.Arg482Gly HEK293 cells transfected with ABCG2-Arg482, ABCG2- R482G, and ABCG2-R482T and plasmid vectors were obtained from Dr. Susan E. Bates (National Cancer Institute, Bethesda, MD). Login to comment 46 ABCG2 p.Arg482Thr ABCG2 p.Arg482Gly Comparable protein expression in the wild-type (Arg482) and mutant (R482G, R482T) ABCG2-transfected cells has been demonstrated by the Bates group (Robey et al., 2003). Login to comment 153 ABCG2 p.Arg482Thr ABCG2 p.Arg482Gly As shown in Fig. 9A, the extent of pH dependence, calculated as the ratio of uptake at pH 5.5 to the uptake at pH 7.4, was approximately 61, 12, and 6 for Arg482 (wild-type BCRP), R482G (mutant BCRP), and R482T (mutant BCRP), respectively. Login to comment 154 ABCG2 p.Arg482Thr ABCG2 p.Arg482Gly A similar trend was observed for MTX; that is, pH-dependent transport was significantly disturbed when positively charged arginine at 482 (Arg482) was replaced by nonionized amino acids (R482G and R482T) at lower pH (Fig. 9B). Login to comment 203 ABCG2 p.Arg482Thr ABCG2 p.Arg482Gly For estrone sulfate, mutant (R482G, R482T) and wild-type (Arg482) BCRP exhibited a similar extent of increase in the transport activity, suggesting that Arg482 was not involved in the pH-dependent transport of estrone sulfate. This is reasonable because the intrinsic pKa of arginine is approximately 12. Login to comment