1h2n: Difference between revisions
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[[Image:1h2n. | [[Image:1h2n.jpg|left|200px]]<br /><applet load="1h2n" size="450" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1h2n" size="450" color="white" frame="true" align="right" spinBox="true" | |||
caption="1h2n, resolution 2.84Å" /> | caption="1h2n, resolution 2.84Å" /> | ||
'''FACTOR INHIBITING HIF-1 ALPHA'''<br /> | '''FACTOR INHIBITING HIF-1 ALPHA'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
1H2N 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 AKG as [http://en.wikipedia.org/wiki/ligands ligands]. | 1H2N 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 AKG as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Site: <scene name='pdbsite=FEA:So4 Binding Site For Chain A'>FEA</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1H2N OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: transcription]] | [[Category: transcription]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 15:54:25 2007'' | ||
Revision as of 16:44, 18 December 2007
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FACTOR INHIBITING HIF-1 ALPHA
OverviewOverview
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 StructureAbout this Structure
1H2N is a Single protein structure of sequence from Homo sapiens with FE2, SO4 and AKG as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
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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