ABCMdb

PMID: 16184031

Woodahl EL, Yang Z, Bui T, Shen DD, Ho RJ
MDR1 G1199A polymorphism alters permeability of HIV protease inhibitors across P-glycoprotein-expressing epithelial cells.
AIDS. 2005 Oct 14;19(15):1617-25., 2005-10-14 [PubMed]

Sentences

No. Mutations Sentence Comment

0 ABCB1 p.Ser400Asn ABCB1 p.Ser400Asn MDR1 G1199A polymorphism alters permeability of HIV protease inhibitors across P-glycoprotein-expressing epithelial cells Erica L. Woodahl, Ziping Yang, Tot Bui, Danny D. Shen and Rodney J.Y. Ho Objective: To evaluate the impact of the human multidrug resistance gene (MDR1) G1199A polymorphism (amino acid change Ser400Asn) on P-glycoprotein (P-gp)- dependent transepithelial permeability and uptake kinetics of HIV protease inhibitors (PI), by using recombinant epithelial cells expressing wild-type MDR1 (MDR1wt ) or the G1199A variant (MDR11199A). Login to comment 29 ABCB1 p.Ser400Asn G1199A results in a serine to asparagine transition at amino acid 400 (Ser400Asn) in a cytoplasmic domain of P-gp, with an allelic frequency of approximately 5.5% in Caucasians [26-28]. Login to comment 135 ABCB1 p.Ser400Asn The mechanisms by which G1199A alters P-gp activity are not yet known. The G1199A polymorphism causes a Ser400Asn, which lies adjacent to the first ATP-binding domain of P-gp and to transmembrane domain 6, one of the transmembrane domains important in substrate binding [32,33]. Login to comment 136 ABCB1 p.Ser400Asn However, because a crystal structure for P-gp is not yet available, the exact orientation of Ser400Asn relative to the substrate-binding regions or ATP-binding domain of P-gp is not known. The G1199A polymorphism may affect ATPase activity of P-gp, altering ATP hydrolysis necessary for substrate efflux. Login to comment