Abstract
The nuclear receptor pregnane X receptor (PXR) plays a key but structurally enigmatic role in human biology. This ligand-regulated transcription factor responds to a diverse array of chemically distinct ligands, including many endogenous compounds and clinical drugs, and regulates the expression of a critical set of protective gene products involved in xenobiotic and endobiotic metabolism. The structural basis of this receptor's remarkable and unique promiscuity is just now coming into focus. We examine the importance of mobile regions novel to the nuclear receptor ligand-binding domain fold in the ability of PXR to respond to a variety of small and large agonists. We also review the functional roles played by PXR in numerous biological pathways and outline emerging areas for the future examination of this key nuclear xenobiotic receptor.
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