1ilh
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(New page: 200px<br /> <applet load="1ilh" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ilh, resolution 2.76Å" /> '''Crystal Structure o...)
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Revision as of 15:24, 12 November 2007
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Crystal Structure of Human Pregnane X Receptor Ligand Binding Domain Bound to SR12813
Contents |
Overview
The human nuclear pregnane X receptor (hPXR) activates cytochrome P450-3A, expression in response to a wide variety of xenobiotics and plays a, critical role in mediating dangerous drug-drug interactions. We present, the crystal structures of the ligand-binding domain of hPXR both alone and, in complex with the cholesterol-lowering drug SR12813 at resolutions of, 2.5 and 2.75 angstroms, respectively. The hydrophobic ligand-binding, cavity of hPXR contains a small number of polar residues, permitting, SR12813 to bind in three distinct orientations. The position and nature of, these polar residues were found to be critical for establishing the, precise pharmacologic activation profile of PXR. Our findings provide, important insights into how hPXR detects xenobiotics and may prove useful, in predicting and avoiding drug-drug interactions.
Disease
Known diseases associated with this structure: Adrenoleukodystrophy, neonatal OMIM:[600414], Zellweger syndrome OMIM:[600414]
About this Structure
1ILH is a Single protein structure of sequence from Homo sapiens with SRL as ligand. Full crystallographic information is available from OCA.
Reference
The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity., Watkins RE, Wisely GB, Moore LB, Collins JL, Lambert MH, Williams SP, Willson TM, Kliewer SA, Redinbo MR, Science. 2001 Jun 22;292(5525):2329-33. Epub 2001 Jun 14. PMID:11408620
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