3ouh

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{{STRUCTURE_3ouh| PDB=3ouh | SCENE= }}
 
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===PHD2-R127 with JNJ41536014===
 
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==Disease==
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==PHD2-R127 with JNJ41536014==
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[[http://www.uniprot.org/uniprot/EGLN1_HUMAN EGLN1_HUMAN]] Defects in EGLN1 are the cause of familial erythrocytosis type 3 (ECYT3) [MIM:[http://omim.org/entry/609820 609820]]. ECYT3 is an autosomal dominant disorder characterized by increased serum red blood cell mass, elevated serum hemoglobin and hematocrit, and normal serum erythropoietin levels.<ref>PMID:16407130</ref><ref>PMID:17579185</ref>
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<StructureSection load='3ouh' size='340' side='right'caption='[[3ouh]], [[Resolution|resolution]] 2.51&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3ouh]] 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=3OUH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OUH 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]] 2.51&#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=014:1-(5-CHLORO-6-FLUORO-1H-BENZIMIDAZOL-2-YL)-1H-PYRAZOLE-4-CARBOXYLIC+ACID'>014</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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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=3ouh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ouh OCA], [https://pdbe.org/3ouh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ouh RCSB], [https://www.ebi.ac.uk/pdbsum/3ouh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ouh ProSAT]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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HIF prolyl 4-hydroxylases (PHD) are a family of enzymes that mediate key physiological responses to hypoxia by modulating the levels of hypoxia inducible factor 1-alpha (HIF1alpha). Certain benzimidazole-2-pyrazole carboxylates were discovered to be PHD2 inhibitors using ligand- and structure-based methods and found to be potent, orally efficacious stimulators of erythropoietin secretion in vivo.
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==Function==
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Benzimidazole-2-pyrazole HIF Prolyl 4-Hydroxylase Inhibitors as Oral Erythropoietin Secretagogues.,Rosen MD, Venkatesan H, Peltier HM, Bembenek SD, Kanelakis KC, Zhao LX, Leonard BE, Hocutt FM, Wu X, Palomino HL, Brondstetter TI, Haugh PV, Cagnon L, Yan W, Liotta LA, Young A, Mirzadegan T, Shankley NP, Barrett TD, Rabinowitz MH ACS Med Chem Lett. 2010 Oct 5;1(9):526-9. doi: 10.1021/ml100198y. eCollection, 2010 Dec 9. PMID:24900242<ref>PMID:24900242</ref>
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[[http://www.uniprot.org/uniprot/EGLN1_HUMAN EGLN1_HUMAN]] Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF1B. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN1 is the most important isozyme under normoxia and, through regulating the stability of HIF1, involved in various hypoxia-influenced processes such as angiogenesis in retinal and cardiac functionality.<ref>PMID:11595184</ref><ref>PMID:12351678</ref><ref>PMID:15897452</ref><ref>PMID:19339211</ref><ref>PMID:21792862</ref>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[3ouh]] 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=3OUH OCA].
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</div>
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<div class="pdbe-citations 3ouh" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
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*[[Hypoxia-inducible factor prolyl hydroxylase|Hypoxia-inducible factor prolyl hydroxylase]]
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*[[Polyl hydroxylase domain 3D structures|Polyl hydroxylase domain 3D structures]]
*[[Prolyl hydroxylase domain|Prolyl hydroxylase domain]]
*[[Prolyl hydroxylase domain|Prolyl hydroxylase domain]]
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== References ==
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==Reference==
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<references/>
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<references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Clark, R.]]
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[[Category: Large Structures]]
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[[Category: Kim, H.]]
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[[Category: Clark R]]
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[[Category: Oxidoreductase]]
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[[Category: Kim H]]
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[[Category: Phd2]]
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Current revision

PHD2-R127 with JNJ41536014

PDB ID 3ouh

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