Molecular Mechanism of Taurocholate Transport by the Bile Salt Export Pump, an ABC Transporter Associated with Intrahepatic Cholestasis.

ABSTRACT: The bile salt export pump (BSEP/ABCB11) transports bile salts from hepatocytes into bile canaliculi. Its malfunction is associated with severe liver disease. One reason for functional impairment of BSEP is systemic administration of drugs, which as a side effect inhibit the transporter. Therefore, drug candidates are routinely screened for potential interaction with this transporter. Hence, understanding the functional biology of BSEP is of key importance. In this study, we engineered the transporter to dissect interdomain communication paths. We introduced mutations in noncanonical and in conserved residues of either of the two nucleotide binding domains and determined the effect on BSEP basal and substrate-stimulated ATPase activity as well as on taurocholate transport. Replacement of th

SUBMITTER: Sohail MI 

PROVIDER: S-EPMC7610612 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature