Pore-exposed tyrosine residues of P-glycoprotein are important hydrogen-bonding partners for drugs.

ABSTRACT: The multispecific efflux transporter, P-glycoprotein, plays an important role in drug disposition. Substrate translocation occurs along the interface of its transmembrane domains. The rotational C2 symmetry of ATP-binding cassette transporters implies the existence of two symmetry-related sets of substrate-interacting amino acids. These sets are identical in homodimeric transporters, and remain evolutionary related in full transporters, such as P-glycoprotein, in which substrates bind preferentially, but nonexclusively, to one of two binding sites. We explored the role of pore-exposed tyrosines for hydrogen-bonding interactions with propafenone type ligands in their preferred binding site 2. Tyrosine 953 is shown to form hydrogen bonds not only with propafenone analogs, but also with the p

SUBMITTER: Donmez Cakil Y 

PROVIDER: S-EPMC4503343 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature