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From Proteopedia
A new crystal structure of the hPXR-LBD in complex with SR12813 (P43212 form)
Structural highlights
FunctionNR1I2_HUMAN Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedThe ligand-binding domain (LBD) of the human nuclear receptor pregnane X receptor (PXR) is known to crystallize in two different crystal forms, P2(1)2(1)2(1) or P4(3)2(1)2, depending on the construct and the strategy used for protein production, as well as the presence or absence of the coactivator-derived peptide SRC-1. In order to facilitate biophysical and structural studies, a versatile construct was designed that allows access to both forms. This was achieved by introducing a thrombin cleavage site between the PXR(LBD) and the SRC-1 peptide fused to its C-terminus. Here, we describe the expression, purification and crystallization processes of this novel construct and report two new structures of PXR(LBD) that were obtained thanks to this strategy. A two-in-one expression construct for biophysical and structural studies of the human pregnane X receptor ligand-binding domain, a pharmaceutical and environmental target.,Carivenc C, Laconde G, Blanc P, Amblard M, Bourguet W, Delfosse V Acta Crystallogr F Struct Biol Commun. 2025 Mar 1. doi: , 10.1107/S2053230X2500069X. PMID:39923198[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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