1iz3: Difference between revisions

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-{{Seed}}
-[[Image:1iz3.png|left|200px]]
-<!--
+==Dimeric structure of FIH (Factor inhibiting HIF)==
-The line below this paragraph, containing "STRUCTURE_1iz3", creates the "Structure Box" on the page.
+<StructureSection load='1iz3' size='340' side='right'caption='[[1iz3]], [[Resolution|resolution]] 2.80&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'>[[1iz3]] 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=1IZ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1IZ3 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]] 2.8&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-{{STRUCTURE_1iz3|  PDB=1iz3  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1iz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1iz3 OCA], [https://pdbe.org/1iz3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1iz3 RCSB], [https://www.ebi.ac.uk/pdbsum/1iz3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1iz3 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/iz/1iz3_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1iz3 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The master switch of cellular hypoxia responses, hypoxia-inducible factor 1 (HIF-1), is hydroxylated by factor inhibiting HIF-1 (FIH-1) at a conserved asparagine residue under normoxia, which suppresses transcriptional activity of HIF-1 by abrogating its interaction with transcription coactivators. Here we report the crystal structure of human FIH-1 at 2.8-A resolution. The structural core of FIH-1 consists of a jellyroll-like beta-barrel containing the conserved ferrous-binding triad residues, confirming that FIH-1 is a member of the 2-oxoglutarate-dependent dioxygenase family. Except for the core structure and triad residues, FIH-1 has many structural deviations from other family members including N- and C-terminal insertions and various deletions in the middle of the structure. The ferrous-binding triad region is highly exposed to the solvent, which is connected to a prominent groove that may bind to a helix near the hydroxylation site of HIF-1. The structure, which is in a dimeric state, also reveals the putative von Hippel-Lindau-binding site that is distinctive to the putative HIF-1-binding site, supporting the formation of the ternary complex by FIH-1, HIF-1, and von Hippel-Lindau. The unique environment of the active site and cofactor-binding region revealed in the structure should allow design of selective drugs that can be used in ischemic diseases to promote hypoxia responses.
-===Dimeric structure of FIH (Factor inhibiting HIF)===
+Structure of human FIH-1 reveals a unique active site pocket and interaction sites for HIF-1 and von Hippel-Lindau.,Lee C, Kim SJ, Jeong DG, Lee SM, Ryu SE J Biol Chem. 2003 Feb 28;278(9):7558-63. Epub 2002 Dec 12. PMID:12482756<ref>PMID:12482756</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1iz3" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_12482756}}, adds the Publication Abstract to the page
+*[[Factor inhibiting HIF|Factor inhibiting HIF]]
-(as it appears on PubMed at http://www.pubmed.gov), where 12482756 is the PubMed ID number.
+*[[Hypoxia-Inducible factor 1 alpha inhibitor|Hypoxia-Inducible factor 1 alpha inhibitor]]
--->
+== References ==
-{{ABSTRACT_PUBMED_12482756}}
+<references/>
+__TOC__
-==About this Structure==
+</StructureSection>
-IZ3 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=1IZ3 OCA].
-==Reference==
-<ref group="xtra">PMID:12482756</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Jeong, D G.]]
+[[Category: Large Structures]]
-[[Category: Kim, S J.]]
+[[Category: Jeong D-G]]
-[[Category: Lee, C.]]
+[[Category: Kim S-J]]
-[[Category: Lee, S M.]]
+[[Category: Lee C]]
-[[Category: Ryu, S E.]]
+[[Category: Lee SM]]
-[[Category: Double beta-sheet helix]]
+[[Category: Ryu S-E]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 13:07:27 2009''