6qgv - Revision history

OCA at 12:00, 24 January 2024

OCA — Wed, 24 Jan 2024 12:00:41 GMT

←Older revision		Revision as of 12:00, 24 January 2024
Line 3:		Line 3:
	<StructureSection load='6qgv' size='340' side='right'caption='[[6qgv]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='6qgv' size='340' side='right'caption='[[6qgv]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6qgv]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QGV OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6QGV FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qgv]] 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=6QGV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QGV FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=J2H:8-[(3-methylpyridin-2-yl)methyl]-3-(4-phenylphenyl)-1-pyrimidin-2-yl-1,3,8-triazaspiro[4.5]decane-2,4-dione'>J2H</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene~~></td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.4Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EGLN1, C1orf12, PNAS-118, PNAS-137 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=J2H:8-[(3-methylpyridin-2-yl)methyl]-3-(4-phenylphenyl)-1-pyrimidin-2-yl-1,3,8-triazaspiro[4.5]decane-2,4-dione'>J2H</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hypoxia-inducible_factor-proline_dioxygenase Hypoxia-inducible factor-proline dioxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.11.29 1.14.11.29] </span></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=6qgv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qgv OCA], [https://pdbe.org/6qgv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qgv RCSB], [https://www.ebi.ac.uk/pdbsum/6qgv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qgv ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6qgv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qgv OCA], [~~http~~://pdbe.org/6qgv PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6qgv RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6qgv PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6qgv ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[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>	+	[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 ==		== Function ==
-	[~~[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>	+	[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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== 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~~.	+	The 2-oxoglutarate (2OG) dependent hypoxia inducible factor (HIF) prolyl hydroxylases (PHDs) are targets for treatment of anaemia and other ischaemia related diseases. PHD inhibitors are in clinical trials; however, the number of reported templates for PHD inhibition is limited. We report structure-activity relationship and crystallographic studies on spiro[4.5]decanone containing PHD inhibitors. Together with other studies, our results reveal spiro[4.5]decanones as useful templates for generation of potent and selective 2OG oxygenase inhibitors.

-	~~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>	+	Studies on spiro[4.5]decanone prolyl hydroxylase domain inhibitors.,Holt-Martyn JP, Tumber A, Rahman MZ, Lippl K, Figg W Jr, McDonough MA, Chowdhury R, Schofield CJ Medchemcomm. 2019 Mar 1;10(4):500-504. doi: 10.1039/c8md00548f. eCollection 2019 , Apr 1. PMID:31057728<ref>PMID:31057728</ref>

	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
Line 24:		Line 23:

	==See Also==		==See Also==
-	*[[~~Prolyl~~ hydroxylase domain\|~~Prolyl~~ hydroxylase domain]]	+	*[[Polyl hydroxylase domain 3D structures\|Polyl hydroxylase domain 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Hypoxia-inducible factor-proline dioxygenase~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Chowdhury, R]]	+	[[Category: Chowdhury R]]
-	[[Category: Holt-Martyn~~, J P~~]]	+	[[Category: Holt-Martyn JP]]
-	[[Category: Rahman~~, M Z~~]]	+	[[Category: Rahman MZ]]
-	[[Category: Schofield~~, C J]]~~	+	[[Category: Schofield CJ]]
-	~~[[Category: 2-oxoglutarate]]~~	+
-	~~[[Category: Beta-hydroxylation]]~~	+
-	~~[[Category: Breast cancer]]~~	+
-	~~[[Category: Cell structure]]~~	+
-	~~[[Category: Cytoplasm]]~~	+
-	~~[[Category: Development]]~~	+
-	~~[[Category: Dna-binding]]~~	+
-	~~[[Category: Dsbh]]~~	+
-	~~[[Category: Egln1]]~~	+
-	~~[[Category: Facial triad]]~~	+
-	~~[[Category: Familial erythrocytosis]]~~	+
-	~~[[Category: Helix-loop-helix-beta]]~~	+
-	~~[[Category: Hif]]~~	+
-	~~[[Category: Hif prolyl hydroxylase domain 2]]~~	+
-	~~[[Category: Hypoxia]]~~	+
-	~~[[Category: Hypoxia-inducible factor]]~~	+
-	~~[[Category: Iron]]~~	+
-	~~[[Category: Metal-binding]]~~	+
-	~~[[Category: Non-heme dioxygenase]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Oxygenase]]~~	+
-	~~[[Category: Phd2]]~~	+
-	~~[[Category: Polymorphism]]~~	+
-	~~[[Category: Signaling]]~~	+
-	~~[[Category: Transcription]]~~	+
-	~~[[Category: Transcription activator/inhibitor]]~~	+
-	~~[[Category: Transcription complex]]~~	+
-	~~[[Category: Transcription/epigenetic regulation]]~~	+
-	~~[[Category: Ubl conjugation]]~~	+
-	~~[[Category: Vitamin c]]~~	+
-	~~[[Category: Zinc-finger~~]]	+

OCA at 08:18, 20 January 2021

OCA — Wed, 20 Jan 2021 08:18:31 GMT

←Older revision		Revision as of 08:18, 20 January 2021
Line 3:		Line 3:
	<StructureSection load='6qgv' size='340' side='right'caption='[[6qgv]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='6qgv' size='340' side='right'caption='[[6qgv]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6qgv]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QGV OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6QGV FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qgv]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QGV OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6QGV FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=J2H:8-[(3-methylpyridin-2-yl)methyl]-3-(4-phenylphenyl)-1-pyrimidin-2-yl-1,3,8-triazaspiro[4.5]decane-2,4-dione'>J2H</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=J2H:8-[(3-methylpyridin-2-yl)methyl]-3-(4-phenylphenyl)-1-pyrimidin-2-yl-1,3,8-triazaspiro[4.5]decane-2,4-dione'>J2H</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EGLN1, C1orf12, PNAS-118, PNAS-137 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hypoxia-inducible_factor-proline_dioxygenase Hypoxia-inducible factor-proline dioxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.11.29 1.14.11.29] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hypoxia-inducible_factor-proline_dioxygenase Hypoxia-inducible factor-proline dioxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.11.29 1.14.11.29] </span></td></tr>
-	<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=6qgv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qgv OCA], [http://pdbe.org/6qgv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qgv RCSB], [http://www.ebi.ac.uk/pdbsum/6qgv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qgv ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6qgv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qgv OCA], [http://pdbe.org/6qgv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qgv RCSB], [http://www.ebi.ac.uk/pdbsum/6qgv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qgv ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 6qgv" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6qgv" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Prolyl hydroxylase domain\|Prolyl hydroxylase domain]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Hypoxia-inducible factor-proline dioxygenase]]		[[Category: Hypoxia-inducible factor-proline dioxygenase]]
	[[Category: Large Structures]]		[[Category: Large Structures]]

OCA at 08:04, 5 February 2020

OCA — Wed, 05 Feb 2020 08:04:49 GMT

←Older revision		Revision as of 08:04, 5 February 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6qgv is ~~ON HOLD~~	+	==HIF prolyl hydroxylase 2 (PHD2/ EGLN1) in complex with a Spiro[4.5]decanone inhibitor (JPHM-2-167)==
		+	<StructureSection load='6qgv' size='340' side='right'caption='[[6qgv]], [[Resolution\|resolution]] 1.40Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6qgv]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QGV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QGV FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=J2H:8-[(3-methylpyridin-2-yl)methyl]-3-(4-phenylphenyl)-1-pyrimidin-2-yl-1,3,8-triazaspiro[4.5]decane-2,4-dione'>J2H</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hypoxia-inducible_factor-proline_dioxygenase Hypoxia-inducible factor-proline dioxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.11.29 1.14.11.29] </span></td></tr>
		+	<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=6qgv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qgv OCA], [http://pdbe.org/6qgv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qgv RCSB], [http://www.ebi.ac.uk/pdbsum/6qgv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qgv ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[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>
		+	== Function ==
		+	[[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>
		+	<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.

-	~~Authors: Chowdhury~~, R., ~~Holt~~-~~Martyn~~, ~~J.P.~~, ~~Rahman~~, M~~.Z.~~, ~~Schofield~~, C.J.	+	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>

-	~~Description: HIF prolyl hydroxylase 2 (PHD2~~/ ~~EGLN1) in complex with~~ a ~~Spiro[4~~.~~5]decanone inhibitor (JPHM~~-2-~~167)~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	[[Category: ~~Rahman, M.Z~~]]	+	<div class="pdbe-citations 6qgv" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Holt-Martyn, J.P~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Hypoxia-inducible factor-proline dioxygenase]]
		+	[[Category: Large Structures]]
	[[Category: Chowdhury, R]]		[[Category: Chowdhury, R]]
-	[[Category: Schofield, C.J]]	+	[[Category: Holt-Martyn, J P]]
		+	[[Category: Rahman, M Z]]
		+	[[Category: Schofield, C J]]
		+	[[Category: 2-oxoglutarate]]
		+	[[Category: Beta-hydroxylation]]
		+	[[Category: Breast cancer]]
		+	[[Category: Cell structure]]
		+	[[Category: Cytoplasm]]
		+	[[Category: Development]]
		+	[[Category: Dna-binding]]
		+	[[Category: Dsbh]]
		+	[[Category: Egln1]]
		+	[[Category: Facial triad]]
		+	[[Category: Familial erythrocytosis]]
		+	[[Category: Helix-loop-helix-beta]]
		+	[[Category: Hif]]
		+	[[Category: Hif prolyl hydroxylase domain 2]]
		+	[[Category: Hypoxia]]
		+	[[Category: Hypoxia-inducible factor]]
		+	[[Category: Iron]]
		+	[[Category: Metal-binding]]
		+	[[Category: Non-heme dioxygenase]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Oxygenase]]
		+	[[Category: Phd2]]
		+	[[Category: Polymorphism]]
		+	[[Category: Signaling]]
		+	[[Category: Transcription]]
		+	[[Category: Transcription activator/inhibitor]]
		+	[[Category: Transcription complex]]
		+	[[Category: Transcription/epigenetic regulation]]
		+	[[Category: Ubl conjugation]]
		+	[[Category: Vitamin c]]
		+	[[Category: Zinc-finger]]

OCA: Protected "6qgv" [edit=sysop:move=sysop]

OCA — Wed, 30 Jan 2019 06:56:13 GMT

Protected "6qgv" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:56, 30 January 2019

OCA: New page: '''Unreleased structure''' The entry 6qgv is ON HOLD Authors: Chowdhury, R., Holt-Martyn, J.P., Rahman, M.Z., Schofield, C.J. Description: HIF prolyl hydroxylase 2 (PHD2/ EGLN1) in com...

OCA — Wed, 30 Jan 2019 06:56:11 GMT

New page: '''Unreleased structure''' The entry 6qgv is ON HOLD Authors: Chowdhury, R., Holt-Martyn, J.P., Rahman, M.Z., Schofield, C.J. Description: HIF prolyl hydroxylase 2 (PHD2/ EGLN1) in com...

New page

'''Unreleased structure'''

The entry 6qgv is ON HOLD

Authors: Chowdhury, R., Holt-Martyn, J.P., Rahman, M.Z., Schofield, C.J.

Description: HIF prolyl hydroxylase 2 (PHD2/ EGLN1) in complex with a Spiro[4.5]decanone inhibitor (JPHM-2-167)
[[Category: Unreleased Structures]]
[[Category: Rahman, M.Z]]
[[Category: Holt-Martyn, J.P]]
[[Category: Chowdhury, R]]
[[Category: Schofield, C.J]]