ABCMdb

PMID: 11013259

Loo TW, Clarke DM
Identification of residues within the drug-binding domain of the human multidrug resistance P-glycoprotein by cysteine-scanning mutagenesis and reaction with dibromobimane.
J Biol Chem. 2000 Dec 15;275(50):39272-8., [PubMed]

Sentences

No. Mutations Sentence Comment

177 ABCB4 p.Ile299Met The mutants L210I, K209E, and I214T in TM4 of mouse mdr3 (31) and I299M (48) and L305A, S, or T in TM5 of human P-gp also changed the substrate specificity of the transporter (49). Login to comment 183 ABCB4 p.Tyr118Cys DBBn also inhibited P-gp by reacting with cysteines in TM2 (Y118C and V125C) and TM8 (S766C). Login to comment 185 ABCB4 p.Tyr118Cys It is possible that some of these residues do not lie within the drug-binding site for these compounds because relatively high concentrations of dBBn were needed to inhibit 50% of the activity of mutants Y118C (TM2) and V125C (TM2) (740 and 870 ␮M, respectively). Login to comment 186 ABCB4 p.Tyr118Cys Another possibility is that modification of mutant Y118C, V125C, or S766C blocks an essential conformational change during coupling of drug binding to ATPase activity. Login to comment