Insights on the structure-function relationship of human multidrug resistance protein 7 (MRP7/ABCC10) from molecular dynamics simulations and docking studies.

ABSTRACT: ATP-binding cassette (ABC) transporters superfamily mediates multidrug resistance in cancer by extruding structurally distinct chemotherapeutic agents, causing failure in chemotherapy. Among the 49 ABC transporters, multidrug resistance protein 7 (MRP7 or ABCC10) is relatively new and has been identified as the efflux pump of multiple anticancer agents including Vinca alkaloids and taxanes. Herein, we construct and validate a homology model for human MRP7 based on the cryo-EM structures of MRP1. Structure-function relationship of MRP7 was obtained from molecular dynamics simulations and docking studies and was in accordance with previous studies of ABC transporters. The motion patterns correlated with efflux mechanism were discussed. Additionally, predicted substrate- and modulator-

SUBMITTER: Wang JQ 

PROVIDER: S-EPMC8491190 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature