2ilm: Difference between revisions

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[[Image:2ilm.jpg|left|200px]]
{{Seed}}
[[Image:2ilm.png|left|200px]]


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{{STRUCTURE_2ilm|  PDB=2ilm  |  SCENE=  }}  
{{STRUCTURE_2ilm|  PDB=2ilm  |  SCENE=  }}  


'''Factor Inhibiting HIF-1 Alpha D201A Mutant in Complex with FE(II), Alpha-Ketoglutarate and HIF-1 Alpha 35mer'''
===Factor Inhibiting HIF-1 Alpha D201A Mutant in Complex with FE(II), Alpha-Ketoglutarate and HIF-1 Alpha 35mer===


==Overview==
The activity of the transcription factor hypoxia-inducible factor (HIF) is regulated by oxygen-dependent hydroxylation. Under normoxic conditions, hydroxylation of proline residues triggers destruction of its alpha-subunit while hydroxylation of Asn(803) in the C-terminal transactivation domain of HIF-1 alpha (CAD) prevents its interaction with p300. Here we report crystal structures of the asparagine hydroxylase (factor-inhibiting HIF, FIH) complexed with Fe((II)), 2-oxoglutarate cosubstrate, and CAD fragments, which reveal the structural basis of HIF modification. CAD binding to FIH occurs via an induced fit process at two distinct interaction sites. At the hydroxylation site CAD adopts a loop conformation, contrasting with a helical conformation for the same residues when bound to p300. Asn(803) of CAD is buried and precisely orientated in the active site such that hydroxylation occurs at its beta-carbon. Together with structures with the inhibitors Zn((II)) and N-oxaloylglycine, analysis of the FIH-CAD complexes will assist design of hydroxylase inhibitors with proangiogenic properties. Conserved structural motifs within FIH imply it is one of an extended family of Fe((II)) oxygenases involved in gene regulation.


==About this Structure==
==About this Structure==
2ILM is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ILM OCA].  
2ILM is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ILM OCA].  


==Reference==
==Reference==
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]
<ref group="xtra">PMID:12446723</ref><ref group="xtra">PMID:15913349</ref><references group="xtra"/>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Peptide-aspartate beta-dioxygenase]]
[[Category: Peptide-aspartate beta-dioxygenase]]
[[Category: Protein complex]]
[[Category: Mcdonough, M A.]]
[[Category: Mcdonough, M A.]]
[[Category: Schofield, C J.]]
[[Category: Schofield, C J.]]
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[[Category: Transcription]]
[[Category: Transcription]]
[[Category: Transcription regulator]]
[[Category: Transcription regulator]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 07:37:51 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 12:09:41 2009''

Revision as of 10:09, 17 February 2009

File:2ilm.png

Template:STRUCTURE 2ilm

Factor Inhibiting HIF-1 Alpha D201A Mutant in Complex with FE(II), Alpha-Ketoglutarate and HIF-1 Alpha 35mer

About this Structure

2ILM is a 2 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

  1. Elkins JM, Hewitson KS, McNeill LA, Seibel JF, Schlemminger I, Pugh CW, Ratcliffe PJ, Schofield CJ. Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alpha. J Biol Chem. 2003 Jan 17;278(3):1802-6. Epub 2002 Nov 21. PMID:12446723 doi:https://dx.doi.org/10.1074/jbc.C200644200
  2. McDonough MA, McNeill LA, Tilliet M, Papamicael CA, Chen QY, Banerji B, Hewitson KS, Schofield CJ. Selective inhibition of factor inhibiting hypoxia-inducible factor. J Am Chem Soc. 2005 Jun 1;127(21):7680-1. PMID:15913349 doi:10.1021/ja050841b

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