2ilm
From Proteopedia
(New page: 200px<br /> <applet load="2ilm" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ilm, resolution 2.30Å" /> '''Factor Inhibiting H...) |
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| - | [[Image:2ilm. | + | [[Image:2ilm.jpg|left|200px]]<br /><applet load="2ilm" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2ilm" size=" | + | |
caption="2ilm, resolution 2.30Å" /> | caption="2ilm, resolution 2.30Å" /> | ||
'''Factor Inhibiting HIF-1 Alpha D201A Mutant in Complex with FE(II), Alpha-Ketoglutarate and HIF-1 Alpha 35mer'''<br /> | '''Factor Inhibiting HIF-1 Alpha D201A Mutant in Complex with FE(II), Alpha-Ketoglutarate and HIF-1 Alpha 35mer'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2ILM is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with FE2, SO4, BCT, AKG and GOL 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:// | + | 2ILM is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=FE2:'>FE2</scene>, <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=BCT:'>BCT</scene>, <scene name='pdbligand=AKG:'>AKG</scene> and <scene name='pdbligand=GOL:'>GOL</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=2ILM OCA]. |
==Reference== | ==Reference== | ||
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[[Category: transcription regulator]] | [[Category: transcription regulator]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:12:16 2008'' |
Revision as of 12:12, 23 January 2008
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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
2ILM is a Protein complex structure of sequences 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
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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