2wa4: Difference between revisions

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-{{Seed}}
-[[Image:2wa4.jpg|left|200px]]
-<!--
+==FACTOR INHIBITING HIF-1 ALPHA WITH N,3-dihydroxybenzamide==
-The line below this paragraph, containing "STRUCTURE_2wa4", creates the "Structure Box" on the page.
+<StructureSection load='2wa4' size='340' side='right'caption='[[2wa4]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2wa4]] 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=2WA4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WA4 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=069:N,3-DIHYDROXYBENZAMIDE'>069</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-{{STRUCTURE_2wa4|  PDB=2wa4  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2wa4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wa4 OCA], [https://pdbe.org/2wa4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wa4 RCSB], [https://www.ebi.ac.uk/pdbsum/2wa4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wa4 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[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>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wa/2wa4_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=2wa4 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Aromatic analogues of the 2-oxoglutarate co-substrate of the hypoxia-inducible factor hydroxylases are shown to bind at the active site iron: Pyridine-2,4-dicarboxylate binds as anticipated with a single molecule chelating the iron in a bidentate manner. The binding mode of a hydroxamic acid analogue, at least in the crystalline state, is unusual because two molecules of the inhibitor are observed at the active site and partial displacement of the iron binding aspartyl residue was observed.
-===FACTOR INHIBITING HIF-1 ALPHA WITH N,3-DIHYDROXYBENZAMIDE===
+Structural basis for binding of cyclic 2-oxoglutarate analogues to factor-inhibiting hypoxia-inducible factor.,Conejo-Garcia A, McDonough MA, Loenarz C, McNeill LA, Hewitson KS, Ge W, Lienard BM, Schofield CJ, Clifton IJ Bioorg Med Chem Lett. 2010 Oct 15;20(20):6125-8. Epub 2010 Aug 10. PMID:20822901<ref>PMID:20822901</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2wa4" style="background-color:#fffaf0;"></div>
-==About this Structure==
+==See Also==
-WA4 is a 1 chain structure with 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=2WA4 OCA].
+*[[Factor inhibiting HIF|Factor inhibiting HIF]]
+*[[Hypoxia-Inducible factor 1 alpha inhibitor|Hypoxia-Inducible factor 1 alpha inhibitor]]
-==Reference==
+== References ==
-<ref group="xtra">PMID:12446723</ref><references group="xtra"/>
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Peptide-aspartate beta-dioxygenase]]
+[[Category: Large Structures]]
-[[Category: Clifton, I J.]]
+[[Category: Clifton IJ]]
-[[Category: Conejo-Garcia, A.]]
+[[Category: Conejo-Garcia A]]
-[[Category: Lienard, B M.R.]]
+[[Category: Lienard BMR]]
-[[Category: Mcdonough, M A.]]
+[[Category: McDonough MA]]
-[[Category: Schofield, C J.]]
+[[Category: Schofield CJ]]
-[[Category: Dioxygenase]]
-[[Category: Hydroxylase]]
-[[Category: Hypoxia]]
-[[Category: Nucleus]]
-[[Category: Oxidoreductase]]
-[[Category: Transcription]]
-[[Category: Transcription activator/inhibitor]]
-[[Category: Transcription regulation]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 21 10:43:18 2010''