4bqy
From Proteopedia
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| - | {{STRUCTURE_4bqy| PDB=4bqy | SCENE= }} | ||
| - | ===HIF prolyl hydroxylase 2 (PHD2/ EGLN1) in complex with Fe(II) and N-[(1-chloro-4-hydroxyisoquinolin-3-yl)carbonyl]alanine=== | ||
| - | {{ABSTRACT_PUBMED_23683440}} | ||
| - | == | + | ==HIF prolyl hydroxylase 2 (PHD2/ EGLN1) in complex with Fe(II) and N-[(1-chloro-4-hydroxyisoquinolin-3-yl)carbonyl]alanine== |
| - | [[http://www.uniprot.org/uniprot/EGLN1_HUMAN EGLN1_HUMAN | + | <StructureSection load='4bqy' size='340' side='right'caption='[[4bqy]], [[Resolution|resolution]] 1.53Å' scene=''> |
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4bqy]] 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=4BQY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BQY FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.53Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=FNT:(2S)-2-{[(1-CHLORO-4-HYDROXYISOQUINOLIN-3-YL)CARBONYL]AMINO}PROPANOIC+ACID'>FNT</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4bqy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bqy OCA], [https://pdbe.org/4bqy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bqy RCSB], [https://www.ebi.ac.uk/pdbsum/4bqy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bqy ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/EGLN1_HUMAN EGLN1_HUMAN] Defects in EGLN1 are the cause of familial erythrocytosis type 3 (ECYT3) [MIM:[https://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> | ||
| + | == Function == | ||
| + | [https://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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The hypoxia inducible factor (HIF) system is central to the signaling of low oxygen (hypoxia) in animals. The levels of HIF-alpha isoforms are regulated in an oxygen-dependent manner by the activity of the HIF prolyl-hydroxylases (PHD or EGLN enzymes), which are Fe(II) and 2-oxoglutarate (2OG) dependent oxygenases. Here, we describe biochemical, crystallographic and cellular profiling studies on PHD inhibitors including selectivity studies using a representative set of human 2OG oxygenases. We identify suitable probe compounds for use in studies on the functional effects of PHD inhibition in cells and in animals. | ||
| - | + | Selective Small Molecule Probes for the Hypoxia Inducible Factor (HIF) Prolyl Hydroxylases.,Chowdhury R, Candela-Lena JI, Chan MC, Greenald DJ, Yeoh KK, Tian YM, McDonough MA, Tumber A, Rose NR, Conejo-Garcia A, Demetriades M, Mathavan S, Kawamura A, Lee MK, van Eeden F, Pugh CW, Ratcliffe PJ, Schofield CJ ACS Chem Biol. 2013 May 17. PMID:23683440<ref>PMID:23683440</ref> | |
| - | + | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| + | <div class="pdbe-citations 4bqy" style="background-color:#fffaf0;"></div> | ||
| - | == | + | ==See Also== |
| - | + | *[[Polyl hydroxylase domain 3D structures|Polyl hydroxylase domain 3D structures]] | |
| - | [[ | + | == References == |
| - | + | <references/> | |
| - | + | __TOC__ | |
| - | + | </StructureSection> | |
| - | + | [[Category: Homo sapiens]] | |
| - | + | [[Category: Large Structures]] | |
| - | + | [[Category: Chowdhury R]] | |
| - | + | [[Category: McDonough MA]] | |
| - | + | [[Category: Schofield CJ]] | |
| - | + | [[Category: Yeoh KK]] | |
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Current revision
HIF prolyl hydroxylase 2 (PHD2/ EGLN1) in complex with Fe(II) and N-[(1-chloro-4-hydroxyisoquinolin-3-yl)carbonyl]alanine
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