6nmq - Revision history

OCA at 14:48, 13 March 2024

OCA — Wed, 13 Mar 2024 14:48:30 GMT

←Older revision		Revision as of 14:48, 13 March 2024
Line 3:		Line 3:
	<StructureSection load='6nmq' size='340' side='right'caption='[[6nmq]], [[Resolution\|resolution]] 1.58Å' scene=''>		<StructureSection load='6nmq' size='340' side='right'caption='[[6nmq]], [[Resolution\|resolution]] 1.58Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6nmq]] 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=6NMQ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6NMQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6nmq]] 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=6NMQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NMQ FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat"~~><scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=KU1:N-(4-oxo-1,4-dihydrocinnoline-3-carbonyl)glycine'>KU1</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]] 1.58Å</td></tr>
-	~~<tr~~ id~~='related'><td class~~="~~sblockLbl~~">~~<b>~~[[~~Related_structure~~\|~~Related:]]</b></td><td class="sblockDat">[[3ouj\|3ouj~~]]</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=KU1:N-(4-oxo-1,4-dihydrocinnoline-3-carbonyl)glycine'>KU1</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6nmq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nmq OCA], [https://pdbe.org/6nmq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nmq RCSB], [https://www.ebi.ac.uk/pdbsum/6nmq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nmq ProSAT]</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=6nmq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nmq OCA], [~~http~~://pdbe.org/6nmq PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6nmq RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6nmq PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6nmq 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;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	A combination of structure-based drug design and medicinal chemistry efforts led us from benzimidazole-2-carboxamide with modestly active hypoxia-inducible factor prolyl hydroxylase 2 inhibition to certain benzimidazole-2-pyrazole carboxylic acids that were more potent as well as orally efficacious stimulators of erythropoietin secretion in our in vivo mouse model. To better understand the structure-activity relationship, it was necessary to account for (i) the complexation of the ligand with the active site Fe(2+), (ii) the strain incurred by the ligand upon binding, and (iii) certain key water interactions identified by a crystal structure analysis. With this more complete computational model, we arrived at an overarching paradigm that accounted for the potency differences between benzimidazole-2-carboxamide and benzimidazole-2-pyrazole carboxylic acid enzyme inhibitors. Moreover, the computational paradigm allowed us to anticipate that the bioisostere replacement strategy (amide --> pyrazole), which had shown success in the benzimidazole series, was not generally applicable to other series. This illustrates that to fully reconcile the important ligand-active site interactions for certain targets, one often needs to move beyond traditional structure-based drug design (such as crystallographic analysis, docking, etc.) and appeal to a higher level of computational theory.	+

-	Beyond Traditional Structure-Based Drug Design: The Role of Iron Complexation, Strain, and Water in the Binding of Inhibitors for Hypoxia-Inducible Factor Prolyl Hydroxylase 2.,Bembenek SD, Venkatesan H, Peltier HM, Rosen MD, Barrett TD, Kanelakis KC, Palomino HL, Brondstetter TI, Mirzadegan T, Rabinowitz MH ACS Omega. 2019 Apr 30;4(4):6703-6708. doi: 10.1021/acsomega.9b00199. Epub 2019, Apr 12. PMID:31179408<ref>PMID:31179408</ref>	+	==See Also==
-		+	*[[Polyl hydroxylase domain 3D structures\|Polyl hydroxylase domain 3D structures]]
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class~~=~~"pdbe-citations 6nmq" style~~=~~"background-color:#fffaf0;"></div>~~	+
	== 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: Bembenek~~, S D~~]]	+	[[Category: Bembenek SD]]
-	[[Category: Mirzadegan, T]]	+	[[Category: Mirzadegan T]]
-	~~[[Category: Cinnoline]]~~	+
-	~~[[Category: Hypoxia-inducible factor prolyl hydroxylase]]~~	+
-	~~[[Category: Iron-containing enzyme]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Phd2~~]]	+

OCA at 07:36, 26 June 2019

OCA — Wed, 26 Jun 2019 07:36:47 GMT

←Older revision		Revision as of 07:36, 26 June 2019
Line 3:		Line 3:
	<StructureSection load='6nmq' size='340' side='right'caption='[[6nmq]], [[Resolution\|resolution]] 1.58Å' scene=''>		<StructureSection load='6nmq' size='340' side='right'caption='[[6nmq]], [[Resolution\|resolution]] 1.58Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6nmq]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NMQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NMQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6nmq]] 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=6NMQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NMQ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=KU1:N-(4-oxo-1,4-dihydrocinnoline-3-carbonyl)glycine'>KU1</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=KU1:N-(4-oxo-1,4-dihydrocinnoline-3-carbonyl)glycine'>KU1</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ouj\|3ouj]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ouj\|3ouj]]</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=6nmq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nmq OCA], [http://pdbe.org/6nmq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nmq RCSB], [http://www.ebi.ac.uk/pdbsum/6nmq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nmq ProSAT]</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=6nmq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nmq OCA], [http://pdbe.org/6nmq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nmq RCSB], [http://www.ebi.ac.uk/pdbsum/6nmq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nmq ProSAT]</span></td></tr>
Line 13:		Line 14:
	== 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>		[[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 ==
		+	A combination of structure-based drug design and medicinal chemistry efforts led us from benzimidazole-2-carboxamide with modestly active hypoxia-inducible factor prolyl hydroxylase 2 inhibition to certain benzimidazole-2-pyrazole carboxylic acids that were more potent as well as orally efficacious stimulators of erythropoietin secretion in our in vivo mouse model. To better understand the structure-activity relationship, it was necessary to account for (i) the complexation of the ligand with the active site Fe(2+), (ii) the strain incurred by the ligand upon binding, and (iii) certain key water interactions identified by a crystal structure analysis. With this more complete computational model, we arrived at an overarching paradigm that accounted for the potency differences between benzimidazole-2-carboxamide and benzimidazole-2-pyrazole carboxylic acid enzyme inhibitors. Moreover, the computational paradigm allowed us to anticipate that the bioisostere replacement strategy (amide --> pyrazole), which had shown success in the benzimidazole series, was not generally applicable to other series. This illustrates that to fully reconcile the important ligand-active site interactions for certain targets, one often needs to move beyond traditional structure-based drug design (such as crystallographic analysis, docking, etc.) and appeal to a higher level of computational theory.
		+
		+	Beyond Traditional Structure-Based Drug Design: The Role of Iron Complexation, Strain, and Water in the Binding of Inhibitors for Hypoxia-Inducible Factor Prolyl Hydroxylase 2.,Bembenek SD, Venkatesan H, Peltier HM, Rosen MD, Barrett TD, Kanelakis KC, Palomino HL, Brondstetter TI, Mirzadegan T, Rabinowitz MH ACS Omega. 2019 Apr 30;4(4):6703-6708. doi: 10.1021/acsomega.9b00199. Epub 2019, Apr 12. PMID:31179408<ref>PMID:31179408</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6nmq" style="background-color:#fffaf0;"></div>
	== 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 07:01, 24 April 2019

OCA — Wed, 24 Apr 2019 07:01:22 GMT

←Older revision		Revision as of 07:01, 24 April 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6nmq is ~~ON HOLD until Paper Publication~~	+	==Hypoxia-Inducible Factor (HIF) Prolyl Hydroxylase 2 (PHD2) in Complex with the Carboxamide Analog JNJ43058171==
-		+	<StructureSection load='6nmq' size='340' side='right'caption='[[6nmq]], [[Resolution\|resolution]] 1.58Å' scene=''>
-	~~Authors~~: ~~Bembenek~~, S.D., ~~Mirzadegan~~, T.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6nmq]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NMQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NMQ FirstGlance]. <br>
-	~~Description~~: ~~Hypoxia~~-~~Inducible Factor~~ (HIF) ~~Prolyl Hydroxylase 2~~ (~~PHD2~~) in ~~Complex~~ with the ~~Carboxamide Analog JNJ43058171~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=KU1:N-(4-oxo-1,4-dihydrocinnoline-3-carbonyl)glycine'>KU1</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ouj\|3ouj]]</td></tr>
-	[[Category: Bembenek, S.D]]	+	<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=6nmq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nmq OCA], [http://pdbe.org/6nmq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nmq RCSB], [http://www.ebi.ac.uk/pdbsum/6nmq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nmq 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>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Hypoxia-inducible factor-proline dioxygenase]]
		+	[[Category: Large Structures]]
		+	[[Category: Bembenek, S D]]
	[[Category: Mirzadegan, T]]		[[Category: Mirzadegan, T]]
		+	[[Category: Cinnoline]]
		+	[[Category: Hypoxia-inducible factor prolyl hydroxylase]]
		+	[[Category: Iron-containing enzyme]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Phd2]]

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

OCA — Wed, 30 Jan 2019 06:36:02 GMT

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

←Older revision

Revision as of 06:36, 30 January 2019

OCA: New page: '''Unreleased structure''' The entry 6nmq is ON HOLD until Paper Publication Authors: Bembenek, S.D., Mirzadegan, T. Description: Hypoxia-Inducible Factor (HIF) Prolyl Hydroxylase 2 (P...

OCA — Wed, 30 Jan 2019 06:36:01 GMT

New page: '''Unreleased structure''' The entry 6nmq is ON HOLD until Paper Publication Authors: Bembenek, S.D., Mirzadegan, T. Description: Hypoxia-Inducible Factor (HIF) Prolyl Hydroxylase 2 (P...

New page

'''Unreleased structure'''

The entry 6nmq is ON HOLD until Paper Publication

Authors: Bembenek, S.D., Mirzadegan, T.

Description: Hypoxia-Inducible Factor (HIF) Prolyl Hydroxylase 2 (PHD2) in Complex with the Carboxamide Analog JNJ43058171
[[Category: Unreleased Structures]]
[[Category: Bembenek, S.D]]
[[Category: Mirzadegan, T]]