2cgo

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{{Seed}}
 
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[[Image:2cgo.png|left|200px]]
 
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==FACTOR INHIBITING HIF-1 ALPHA with fumarate==
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The line below this paragraph, containing "STRUCTURE_2cgo", creates the "Structure Box" on the page.
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<StructureSection load='2cgo' size='340' side='right'caption='[[2cgo]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2cgo]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CGO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CGO FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=FUM:FUMARIC+ACID'>FUM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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{{STRUCTURE_2cgo| PDB=2cgo | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2cgo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cgo OCA], [https://pdbe.org/2cgo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cgo RCSB], [https://www.ebi.ac.uk/pdbsum/2cgo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cgo ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/HIF1N_HUMAN HIF1N_HUMAN] Hydroxylates HIF-1 alpha at 'Asp-803' in the C-terminal transactivation domain (CAD). Functions as an oxygen sensor and, under normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300-interacting transactivator. Involved in transcriptional repression through interaction with HIF1A, VHL and histone deacetylases. Hydroxylates specific Asn residues within ankyrin repeat domains (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A and several other ARD-containing proteins. Also hydroxylates Asp and His residues within ARDs of ANK1 and TNKS2, respectively. Negatively regulates NOTCH1 activity, accelerating myogenic differentiation. Positively regulates ASB4 activity, promoting vascular differentiation.<ref>PMID:12080085</ref> <ref>PMID:12042299</ref> <ref>PMID:17003112</ref> <ref>PMID:18299578</ref> <ref>PMID:19245366</ref> <ref>PMID:17573339</ref> <ref>PMID:21251231</ref> <ref>PMID:21177872</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cg/2cgo_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2cgo ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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===FACTOR INHIBITING HIF-1 ALPHA WITH FUMARATE===
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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<ref>PMID:17135241</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2cgo" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_17135241}}, adds the Publication Abstract to the page
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*[[Factor inhibiting HIF|Factor inhibiting HIF]]
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(as it appears on PubMed at http://www.pubmed.gov), where 17135241 is the PubMed ID number.
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*[[Hypoxia-Inducible factor 1 alpha inhibitor|Hypoxia-Inducible factor 1 alpha inhibitor]]
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== References ==
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{{ABSTRACT_PUBMED_17135241}}
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<references/>
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__TOC__
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==About this Structure==
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</StructureSection>
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2CGO is a 1 chain structure of sequence 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=2CGO OCA].
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==Reference==
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<ref group="xtra">PMID:17135241</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Peptide-aspartate beta-dioxygenase]]
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[[Category: Large Structures]]
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[[Category: Clifton, I J.]]
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[[Category: Clifton IJ]]
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[[Category: Mcdonough, M A.]]
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[[Category: McDonough MA]]
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[[Category: Schofield, C J.]]
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[[Category: Schofield CJ]]
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[[Category: 2-oxoglutarate]]
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[[Category: Acetylation]]
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[[Category: Activator]]
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[[Category: Alternative splicing]]
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[[Category: Asparaginyl hydroxylase]]
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[[Category: Dioxygenase]]
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[[Category: Dna-binding]]
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[[Category: Dsbh]]
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[[Category: Fi]]
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[[Category: Hif]]
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[[Category: Hydroxylation]]
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[[Category: Hypoxia]]
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[[Category: Iron]]
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[[Category: Metal-binding]]
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[[Category: Nuclear protein]]
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[[Category: Oxidoreductase]]
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[[Category: Oxygenase]]
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[[Category: Phosphorylation]]
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[[Category: Polymorphism]]
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[[Category: S-nitrosylation]]
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[[Category: Transcription]]
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[[Category: Transcription activator/inhibitor]]
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[[Category: Transcription regulation]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 13:54:29 2009''
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Current revision

FACTOR INHIBITING HIF-1 ALPHA with fumarate

PDB ID 2cgo

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