2cgo: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:2cgo.jpg|left|200px]]<br /><applet load="2cgo" size=" | [[Image:2cgo.jpg|left|200px]]<br /><applet load="2cgo" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="2cgo, resolution 2.30Å" /> | caption="2cgo, resolution 2.30Å" /> | ||
'''FACTOR INHIBITING HIF-1 ALPHA WITH FUMARATE'''<br /> | '''FACTOR INHIBITING HIF-1 ALPHA WITH FUMARATE'''<br /> | ||
| Line 7: | Line 7: | ||
==About this Structure== | ==About this Structure== | ||
2CGO 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 FE, SO4 and FMR 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] Known structural/functional Site: <scene name='pdbsite=AC1:So4 Binding Site For Chain A'>AC1</scene>. Full crystallographic information is available from [http:// | 2CGO 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=FE:'>FE</scene>, <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=FMR:'>FMR</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] Known structural/functional Site: <scene name='pdbsite=AC1:So4+Binding+Site+For+Chain+A'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CGO OCA]. | ||
==Reference== | ==Reference== | ||
| Line 44: | Line 44: | ||
[[Category: transcription regulation]] | [[Category: transcription regulation]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 10:35:06 2008'' | ||
Revision as of 11:35, 3 February 2008
|
FACTOR INHIBITING HIF-1 ALPHA WITH FUMARATE
OverviewOverview
In humans both the levels and activity of the alpha-subunit of the, hypoxia-inducible transcription factor (HIF-alpha) are regulated by its, post-translation hydroxylation as catalyzed by iron- and 2-oxoglutarate, (2OG)-dependent prolyl and asparaginyl hydroxylases (PHD1-3 and, factor-inhibiting HIF (FIH), respectively). One consequence of hypoxia is, the accumulation of tricarboxylic acid cycle intermediates (TCAIs). In, vitro assays were used to assess non-2OG TCAIs as inhibitors of purified, PHD2 and FIH. Under the assay conditions, no significant FIH inhibition, was observed by the TCAIs or pyruvate, but fumarate, succinate, and, isocitrate inhibited PHD2. Mass spectrometric analyses under nondenaturing, conditions were used to investigate the binding of TCAIs to PHD2 and, supported the solution studies. X-ray crystal structures of FIH in complex, with Fe(II) and fumarate or succinate revealed similar binding modes for, each in the 2OG co-substrate binding site. The in vitro results suggest, that the cellular inhibition of PHD2, but probably not FIH, by fumarate, and succinate may play a role in the Warburg effect providing that, appropriate relative concentrations of the components are achieved under, physiological conditions.
About this StructureAbout this Structure
2CGO 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 Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
Structural and mechanistic studies on the inhibition of the hypoxia-inducible transcription factor hydroxylases by tricarboxylic acid cycle intermediates., Hewitson KS, Lienard BM, McDonough MA, Clifton IJ, Butler D, Soares AS, Oldham NJ, McNeill LA, Schofield CJ, J Biol Chem. 2007 Feb 2;282(5):3293-301. Epub 2006 Nov 29. PMID:17135241
Page seeded by OCA on Sun Feb 3 10:35:06 2008
Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Pages with broken file links
- Homo sapiens
- Peptide-aspartate beta-dioxygenase
- Single protein
- Clifton, I.J.
- Mcdonough, M.A.
- Schofield, C.J.
- FE
- FMR
- SO4
- 2-oxoglutarate
- Acetylation
- Activator
- Alternative splicing
- Asparaginyl hydroxylase
- Dioxygenase
- Dna-binding
- Dsbh
- Fi
- Hif
- Hydroxylation
- Hypoxia
- Iron
- Metal-binding
- Nuclear protein
- Oxidoreductase
- Oxygenase
- Phosphorylation
- Polymorphism
- S-nitrosylation
- Transcription
- Transcription activator/inhibitor
- Transcription regulation