Exploration of the conformational landscape in pregnane X receptor reveals a new binding pocket.

ABSTRACT: Ligand-regulated pregnane X receptor (PXR), a member of the nuclear receptor superfamily, plays a central role in xenobiotic metabolism. Despite its critical role in drug metabolism, PXR activation can lead to adverse drug-drug interactions and early stage metabolism of drugs. Activated PXR can induce cancer drug resistance and enhance the onset of malignancy. Since promiscuity in ligand binding makes it difficult to develop competitive inhibitors targeting PXR ligand binding pocket (LBP), it is essential to identify allosteric sites for effective PXR antagonism. Here, molecular dynamics (MD) simulation studies unravelled the existence of two different conformational states, namely "expanded" and "contracted", in apo PXR ligand binding domain (LBD). Ligand binding events shifted this confo

SUBMITTER: Chandran A 

PROVIDER: S-EPMC5079256 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature