1ilh
From Proteopedia
(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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| - | [[Image:1ilh.gif|left|200px]]<br /> | + | [[Image:1ilh.gif|left|200px]]<br /><applet load="1ilh" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1ilh" size=" | + | |
caption="1ilh, resolution 2.76Å" /> | caption="1ilh, resolution 2.76Å" /> | ||
'''Crystal Structure of Human Pregnane X Receptor Ligand Binding Domain Bound to SR12813'''<br /> | '''Crystal Structure of Human Pregnane X Receptor Ligand Binding Domain Bound to SR12813'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The human nuclear pregnane X receptor (hPXR) activates cytochrome P450-3A | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1ILH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SRL as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1ILH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SRL:'>SRL</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ILH OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Redinbo, M | + | [[Category: Redinbo, M R.]] |
| - | [[Category: Watkins, R | + | [[Category: Watkins, R E.]] |
[[Category: SRL]] | [[Category: SRL]] | ||
[[Category: ligand]] | [[Category: ligand]] | ||
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[[Category: xenobiotic]] | [[Category: xenobiotic]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:13:04 2008'' |
Revision as of 11:13, 21 February 2008
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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 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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