Reaction dynamics of ATP hydrolysis catalyzed by P-glycoprotein.

ABSTRACT: P-glycoprotein (P-gp) is a member of the ABC transporter family that confers drug resistance to many tumors by catalyzing their efflux, and it is a major component of drug-drug interactions. P-gp couples drug efflux with ATP hydrolysis by coordinating conformational changes in the drug binding sites with the hydrolysis of ATP and release of ADP. To understand the relative rates of the chemical step for hydrolysis and the conformational changes that follow it, we exploited isotope exchange methods to determine the extent to which the ATP hydrolysis step is reversible. With γ(18)O4-labeled ATP, no positional isotope exchange is detectable at the bridging β-phosphorus-O-γ-phosphorus bond. Furthermore, the phosphate derived from hydrolysis includes a constant ratio of three (18)O/two (18)O/one

SUBMITTER: Scian M 

PROVIDER: S-EPMC3985762 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature