Study of Allosteric Transitions of Human P-Glycoprotein by Using the Two-State Anisotropic Network Model.

ABSTRACT: Human P-glycoprotein (P-gp) is a kind of ATP-binding cassette (ABC) transporters. Once human P-gp is overexpressed in tumor cells, which can lead to tumor multidrug resistance (MDR). However, the present experimental methods are difficult to obtain the large-scale conformational transition process of human P-gp. In this work, we explored the allosteric pathway of human P-gp from the inward-facing (IF) to the outward-facing (OF) state in the substrate transport process with the two-state anisotropic network model (tANM). These results suggest that the allosteric transitions proceed in a coupled way. The conformational changes of nucleotide-binding domains (NBDs) finally make the transmembrane domains (TMDs) to the OF state via the role of the allosteric propagation of the intracellul

SUBMITTER: Li H 

PROVIDER: S-EPMC8863969 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature