2y0i

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[[Image:2y0i.png|left|200px]]
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==FACTOR INHIBITING HIF-1 ALPHA IN COMPLEX WITH TANKYRASE-2 (TNKS2) FRAGMENT PEPTIDE (21-MER)==
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<StructureSection load='2y0i' size='340' side='right' caption='[[2y0i]], [[Resolution|resolution]] 2.28&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2y0i]] is a 2 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=2Y0I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Y0I FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2wa4|2wa4]], [[1mze|1mze]], [[2w0x|2w0x]], [[2cgn|2cgn]], [[1mzf|1mzf]], [[2wa3|2wa3]], [[1yci|1yci]], [[1h2n|1h2n]], [[1h2k|1h2k]], [[2cgo|2cgo]], [[1iz3|1iz3]], [[2xum|2xum]], [[1h2l|1h2l]], [[1h2m|1h2m]]</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2y0i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y0i OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2y0i RCSB], [http://www.ebi.ac.uk/pdbsum/2y0i PDBsum]</span></td></tr>
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</table>
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== Function ==
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[[http://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> [[http://www.uniprot.org/uniprot/TNKS2_HUMAN TNKS2_HUMAN]] Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates poly-ADP-ribosylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates poly-ADP-ribosylation of TERF1, thereby contributing to the regulation of telomere length. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles.<ref>PMID:11802774</ref> <ref>PMID:11739745</ref> <ref>PMID:19759537</ref> <ref>PMID:21478859</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Factor-inhibiting hypoxia-inducible factor (FIH) is an Fe(II)/2-oxoglutarate-dependent dioxygenase that acts as a negative regulator of the hypoxia-inducible factor (HIF) by catalysing beta-hydroxylation of an asparaginyl residue in its C-terminal transcriptional activation domain (CAD). In addition to the HIF-CAD, FIH also catalyses asparaginyl hydroxylation of many ankyrin repeat domain (ARD)-containing proteins, revealing a broad sequence selectivity. However, there are few reports on the selectivity of FIH for the hydroxylation of specific residues. Here we report that histidinyl-residues within the ARD of tankyrase-2 can be hydroxylated by FIH. NMR and crystallographic analyses show that the histidinyl hydroxylation occurs at the beta-position. The results further expand the scope of FIH-catalysed hydroxylations.
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{{STRUCTURE_2y0i| PDB=2y0i | SCENE= }}
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Factor-Inhibiting Hypoxia-Inducible Factor (FIH) Catalyses the Posttranslational Hydroxylation of Histidinyl Residues within Ankyrin Repeat Domains.,Yang M, Chowdhury R, Ge W, Hamed RB, McDonough MA, Claridge TD, Kessler BM, Cockman ME, Ratcliffe PJ, Schofield CJ FEBS J. 2011 Jan 20. doi: 10.1111/j.1742-4658.2011.08022.x. PMID:21251231<ref>PMID:21251231</ref>
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===FACTOR INHIBITING HIF-1 ALPHA IN COMPLEX WITH TANKYRASE-2 (TNKS2) FRAGMENT PEPTIDE (21-MER)===
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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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{{ABSTRACT_PUBMED_21251231}}
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==About this Structure==
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[[2y0i]] is a 2 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=2Y0I OCA].
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==See Also==
==See Also==
*[[Factor inhibiting HIF|Factor inhibiting HIF]]
*[[Factor inhibiting HIF|Factor inhibiting HIF]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:021251231</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Peptide-aspartate beta-dioxygenase]]
[[Category: Peptide-aspartate beta-dioxygenase]]
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[[Category: Chowdhury, R.]]
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[[Category: Chowdhury, R]]
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[[Category: Mcdonough, M A.]]
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[[Category: Mcdonough, M A]]
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[[Category: Schofield, C J.]]
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[[Category: Schofield, C J]]
[[Category: Ankyrin repeat domain]]
[[Category: Ankyrin repeat domain]]
[[Category: Asparaginyl/aspartyl hydroxylase]]
[[Category: Asparaginyl/aspartyl hydroxylase]]

Revision as of 12:36, 25 December 2014

FACTOR INHIBITING HIF-1 ALPHA IN COMPLEX WITH TANKYRASE-2 (TNKS2) FRAGMENT PEPTIDE (21-MER)

2y0i, resolution 2.28Å

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