ABCMdb

PMID: 16981002

Clark R, Kerr ID, Callaghan R
Multiple drugbinding sites on the R482G isoform of the ABCG2 transporter.
Br J Pharmacol. 2006 Nov;149(5):506-15. Epub 2006 Sep 18., [PubMed]

Sentences

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0 ABCG2 p.Arg482Gly RESEARCH PAPER Multiple drugbinding sites on the R482G isoform of the ABCG2 transporter R Clark1 , ID Kerr2 and R Callaghan1 1 Nuffield Department of Clinical Laboratory Sciences, University of Oxford, UK and 2 Centre for Biochemistry and Cell Biology, School of Biomedical Sciences, University of Nottingham, UK Background & Purpose: Drug-resistant cancer cells frequently display efflux pumps such as P-glycoprotein (P-gp), the multidrug resistance associated protein (MRP1) or the transporter ABCG2. Login to comment 42 ABCG2 p.Arg482Gly The objective is to provide the mechanism underlying multidrug recognition by the R482G isoform (ABCG2R482G ) by examination of the number of drug-binding sites and whether competitive or allosteric interactions exist between substrates on the transporter. Login to comment 43 ABCG2 p.Arg482Gly The R482G isoform was chosen for these investigations because of its wider pharmacological spectrum, thereby enabling a more exhaustive characterization of drug binding to the transporter. Login to comment 112 ABCG2 p.Arg482Gly Membranes expressing the R482G isoform of ABCG2 containing an N-terminal hexahistidine tag were incubated in the presence of varying [3 H]daunomycin concentrations. Login to comment 161 ABCG2 p.Arg482Gly This was achieved initially with heterologous displacement assays using compounds previously demonstrated to interact with the R482G isoform of ABCG2 (primarily through steady-state accumulation and ATPase assays). Login to comment 165 ABCG2 p.Arg482Gly Mitoxantrone is one of the few compounds demonstrated to interact with both the wild-type and R482G mutant isoforms of ABCG2 (Mitomo et al., 2003; Sarkadi et al., 2004). Login to comment 213 ABCG2 p.Arg482Gly How does our binding data compare to the existing data on transport of drugs by both wild-type and R482G ABCG2? Login to comment 252 ABCG2 p.Arg482Gly Further studies will also be required to compare the binding of drugs to wild-type ABCG2 and the data obtained with the R482G isoform will be useful in eventually describing the location and molecular properties of drug interactions with this transporter. Login to comment