ABCMdb

PMID: 18657189

McDevitt CA, Crowley E, Hobbs G, Starr KJ, Kerr ID, Callaghan R
Is ATP binding responsible for initiating drug translocation by the multidrug transporter ABCG2?
FEBS J. 2008 Sep;275(17):4354-62. Epub 2008 Jul 24., [PubMed]

Sentences

No. Mutations Sentence Comment

27 ABCG2 p.Arg482Thr ABCG2 p.Arg482Gly Selection in mitoxantrone produced R482G or R482T point mutations that present considerably broader substrate selectivity [20,21]. Login to comment 28 ABCG2 p.Arg482Gly For example, the R482G isoform is a gain-of-function mutation which mediates the transport of doxorubicin, daunomycin and rhodamine 123, whereas it has a loss of function with respect to methotrexate transport. Login to comment 31 ABCG2 p.Arg482Gly In a departure from the drug-protein interactions with ABCB1, the R482G isoform also contains multiple sites of interaction for a single drug (daunomycin), which can manifest as homotropic allostery [22]. Login to comment 34 ABCG2 p.Arg482Gly The best evidence for an interaction between the two domains is the ability of numerous substrates and modulators of ABCG2 (and the R482G isoform) to stimulate the rate of ATP hydrolysis [21,24,25], albeit to a lesser degree than that commonly encountered with ABCB1. Login to comment