1yci
From Proteopedia
(New page: 200px<br /> <applet load="1yci" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yci, resolution 2.70Å" /> '''Factor inhibiting H...) |
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| - | [[Image:1yci.gif|left|200px]]<br /> | + | [[Image:1yci.gif|left|200px]]<br /><applet load="1yci" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1yci" size=" | + | |
caption="1yci, resolution 2.70Å" /> | caption="1yci, resolution 2.70Å" /> | ||
'''Factor inhibiting HIF-1 alpha in complex with N-(carboxycarbonyl)-D-phenylalanine'''<br /> | '''Factor inhibiting HIF-1 alpha in complex with N-(carboxycarbonyl)-D-phenylalanine'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A set of four non-heme iron(II) and 2-oxoglutarate-dependent enzymes catalyze the post-translational modification of a transcription factor, hypoxia inducible factor (HIF), that mediates the hypoxic response in animals. Hydroxylation of HIF both causes its degradation and limits its activity. We describe how the use of structural data coupled to solid-phase synthesis led to the discovery of a selective inhibitor of one of the HIF hydroxylases. The inhibitor N-oxalyl- | + | A set of four non-heme iron(II) and 2-oxoglutarate-dependent enzymes catalyze the post-translational modification of a transcription factor, hypoxia inducible factor (HIF), that mediates the hypoxic response in animals. Hydroxylation of HIF both causes its degradation and limits its activity. We describe how the use of structural data coupled to solid-phase synthesis led to the discovery of a selective inhibitor of one of the HIF hydroxylases. The inhibitor N-oxalyl-d-phenylalanine was shown to inhibit the HIF asparaginyl hydroxylase (FIH) but not a HIF prolyl hydroxylase. A crystal structure of the inhibitor complexed to FIH reveals that it binds in the 2OG and, likely, in the dioxygen binding site. The results will help to enable the modulation of the hypoxic response for the up-regulation of specific genes of biomedical importance, such as erythropoietin and vascular endothelial growth factor. |
==About this Structure== | ==About this Structure== | ||
| - | 1YCI 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 FE2, SO4 and NDF as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Peptide-aspartate_beta-dioxygenase Peptide-aspartate beta-dioxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.11.16 1.14.11.16] Full crystallographic information is available from [http:// | + | 1YCI 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=FE2:'>FE2</scene>, <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=NDF:'>NDF</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Peptide-aspartate_beta-dioxygenase Peptide-aspartate beta-dioxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.11.16 1.14.11.16] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YCI OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Peptide-aspartate beta-dioxygenase]] | [[Category: Peptide-aspartate beta-dioxygenase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: McDonough, M | + | [[Category: McDonough, M A.]] |
| - | [[Category: Schofield, C | + | [[Category: Schofield, C J.]] |
[[Category: FE2]] | [[Category: FE2]] | ||
[[Category: NDF]] | [[Category: NDF]] | ||
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[[Category: transcription]] | [[Category: transcription]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:03:55 2008'' |
Revision as of 14:03, 21 February 2008
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Factor inhibiting HIF-1 alpha in complex with N-(carboxycarbonyl)-D-phenylalanine
Overview
A set of four non-heme iron(II) and 2-oxoglutarate-dependent enzymes catalyze the post-translational modification of a transcription factor, hypoxia inducible factor (HIF), that mediates the hypoxic response in animals. Hydroxylation of HIF both causes its degradation and limits its activity. We describe how the use of structural data coupled to solid-phase synthesis led to the discovery of a selective inhibitor of one of the HIF hydroxylases. The inhibitor N-oxalyl-d-phenylalanine was shown to inhibit the HIF asparaginyl hydroxylase (FIH) but not a HIF prolyl hydroxylase. A crystal structure of the inhibitor complexed to FIH reveals that it binds in the 2OG and, likely, in the dioxygen binding site. The results will help to enable the modulation of the hypoxic response for the up-regulation of specific genes of biomedical importance, such as erythropoietin and vascular endothelial growth factor.
About this Structure
1YCI is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Peptide-aspartate beta-dioxygenase, with EC number 1.14.11.16 Full crystallographic information is available from OCA.
Reference
Selective inhibition of factor inhibiting hypoxia-inducible factor., McDonough MA, McNeill LA, Tilliet M, Papamicael CA, Chen QY, Banerji B, Hewitson KS, Schofield CJ, J Am Chem Soc. 2005 Jun 1;127(21):7680-1. PMID:15913349
Page seeded by OCA on Thu Feb 21 16:03:55 2008
Categories: Homo sapiens | Peptide-aspartate beta-dioxygenase | Single protein | McDonough, M A. | Schofield, C J. | FE2 | NDF | SO4 | Asparaginyl hydroxylase | Dsbh | Fih | Hif | Hydroxylase n-(carboxycarbonyl)-d-phenylalanine | Hypoxia | Inhibitor 2-oxoglutarate | Ndf | Nofd | Oxygenase | Transcription
