Molecular basis of the polyspecificity of P-glycoprotein (ABCB1): recent biochemical and structural studies.

ABSTRACT: ABCB1 (P-glycoprotein/P-gp) is an ATP-binding cassette transporter well known for its association with multidrug resistance in cancer cells. Powered by the hydrolysis of ATP, it effluxes structurally diverse compounds. In this chapter, we discuss current views on the molecular basis of the substrate polyspecificity of P-gp. One of the features that accounts for this property is the structural flexibility observed in P-gp. Several X-ray crystal structures of mouse P-gp have been published recently in the absence of nucleotide, with and without bound inhibitors. All the structures are in an inward-facing conformation exhibiting different degrees of domain separation, thus revealing a highly flexible protein. Biochemical and biophysical studies also demonstrate this flexibility in mouse as we

SUBMITTER: Chufan EE 

PROVIDER: S-EPMC7709800 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature