Catalytic transitions in the human MDR1 P-glycoprotein drug binding sites.

ABSTRACT: Multidrug resistance proteins that belong to the ATP-binding cassette family like the human P-glycoprotein (ABCB1 or Pgp) are responsible for many failed cancer and antiviral chemotherapies because these membrane transporters remove the chemotherapeutics from the targeted cells. Understanding the details of the catalytic mechanism of Pgp is therefore critical to the development of inhibitors that might overcome these resistances. In this work, targeted molecular dynamics techniques were used to elucidate catalytically relevant structures of Pgp. Crystal structures of homologues in four different conformations were used as intermediate targets in the dynamics simulations. Transitions from conformations that were wide open to the cytoplasm to transition state conformations that were wide ope

SUBMITTER: Wise JG 

PROVIDER: S-EPMC3383123 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature