1yci

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[[Image:1yci.gif|left|200px]]
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{{STRUCTURE_1yci| PDB=1yci | SCENE= }}
{{STRUCTURE_1yci| PDB=1yci | SCENE= }}
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'''Factor inhibiting HIF-1 alpha in complex with N-(carboxycarbonyl)-D-phenylalanine'''
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===Factor inhibiting HIF-1 alpha in complex with N-(carboxycarbonyl)-D-phenylalanine===
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==Overview==
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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.
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The line below this paragraph, {{ABSTRACT_PUBMED_15913349}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 15913349 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15913349}}
==About this Structure==
==About this Structure==
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==Reference==
==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:[http://www.ncbi.nlm.nih.gov/pubmed/15913349 15913349]
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:[http://www.ncbi.nlm.nih.gov/pubmed/15913349 15913349]
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Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alpha., Elkins JM, Hewitson KS, McNeill LA, Seibel JF, Schlemminger I, Pugh CW, Ratcliffe PJ, Schofield CJ, J Biol Chem. 2003 Jan 17;278(3):1802-6. Epub 2002 Nov 21. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12446723 12446723]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Peptide-aspartate beta-dioxygenase]]
[[Category: Peptide-aspartate beta-dioxygenase]]
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[[Category: Oxygenase]]
[[Category: Oxygenase]]
[[Category: Transcription]]
[[Category: Transcription]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 16:09:13 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 04:59:09 2008''

Revision as of 01:59, 28 July 2008

Image:1yci.png

Template:STRUCTURE 1yci

Factor inhibiting HIF-1 alpha in complex with N-(carboxycarbonyl)-D-phenylalanine

Template:ABSTRACT PUBMED 15913349

About this Structure

1YCI is a Single protein structure of sequence from Homo sapiens. 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

Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alpha., Elkins JM, Hewitson KS, McNeill LA, Seibel JF, Schlemminger I, Pugh CW, Ratcliffe PJ, Schofield CJ, J Biol Chem. 2003 Jan 17;278(3):1802-6. Epub 2002 Nov 21. PMID:12446723

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