Conformational analysis of human ATP-binding cassette transporter ABCB1 in lipid nanodiscs and inhibition by the antibodies MRK16 and UIC2.

ABSTRACT: The human ATP-binding cassette (ABC) transporter, P-glycoprotein (P-gp; ABCB1), mediates the ATP-dependent efflux of a variety of drugs. As a result, P-gp plays a critical role in tumor cell drug resistance and the pharmacokinetic properties of most drugs. P-gp exhibits extraordinary substrate and inhibitor promiscuity, resulting in a wide range of possible drug-drug interactions. Inhibitory antibodies have long been considered as a possible strategy to modulate P-gp-dependent cancer cell drug resistance, and it is widely suggested that the antibodies MRK16 and UIC2 inhibit P-gp by capturing a single isoform and preventing flux through the catalytic cycle. Although the crystal structures of many bacterial whole transporters, as well as isolated nucleotide-binding domains, have been solved,

SUBMITTER: Ritchie TK 

PROVIDER: S-EPMC3234772 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature