6zbo - Revision history

OCA at 13:45, 24 January 2024

OCA — Wed, 24 Jan 2024 13:45:57 GMT

←Older revision		Revision as of 13:45, 24 January 2024
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	<StructureSection load='6zbo' size='340' side='right'caption='[[6zbo]], [[Resolution\|resolution]] 1.79Å' scene=''>		<StructureSection load='6zbo' size='340' side='right'caption='[[6zbo]], [[Resolution\|resolution]] 1.79Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6zbo]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZBO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZBO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6zbo]] is a 6 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=6ZBO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZBO FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=QEQ:2-(6-morpholin-4-ylpyrimidin-4-yl)-4-(1,2,3-triazol-1-yl)pyrazol-3-ol'>QEQ</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]] 1.79Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EGLN1, C1orf12, PNAS-118, PNAS-137 ([https://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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=QEQ:2-(6-morpholin-4-ylpyrimidin-4-yl)-4-(1,2,3-triazol-1-yl)pyrazol-3-ol'>QEQ</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Hypoxia-inducible_factor-proline_dioxygenase Hypoxia-inducible factor-proline dioxygenase], with EC number [https://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=6zbo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zbo OCA], [https://pdbe.org/6zbo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zbo RCSB], [https://www.ebi.ac.uk/pdbsum/6zbo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zbo ProSAT]</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=6zbo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zbo OCA], [https://pdbe.org/6zbo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zbo RCSB], [https://www.ebi.ac.uk/pdbsum/6zbo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zbo ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== 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>	+	[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 ==
-	[[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>	+	[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 ==
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	</div>		</div>
	<div class="pdbe-citations 6zbo" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6zbo" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[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: ~~Holt-Martyn, J P~~]]	+	[[Category: Figg Jr WD]]
-	[[Category: ~~Jr, W D.Figg~~]]	+	[[Category: Holt-Martyn JP]]
-	[[Category: McDonough~~, M A~~]]	+	[[Category: McDonough MA]]
-	[[Category: Nakashima, Y]]	+	[[Category: Nakashima Y]]
-	[[Category: Schofield~~, C J]]~~	+	[[Category: Schofield CJ]]
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Hif]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Molidustat]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Phd2~~]]	+

OCA at 05:48, 6 October 2021

OCA — Wed, 06 Oct 2021 05:48:52 GMT

←Older revision		Revision as of 05:48, 6 October 2021
Line 1:		Line 1:

	==HIF Prolyl Hydroxylase 2 (PHD2/EGLN1) in Complex with 1-(6-morpholinopyrimidin-4-yl)-4-(1H-1,2,3-triazol-1-yl)-1H-pyrazol-5-ol (Molidustat)==		==HIF Prolyl Hydroxylase 2 (PHD2/EGLN1) in Complex with 1-(6-morpholinopyrimidin-4-yl)-4-(1H-1,2,3-triazol-1-yl)-1H-pyrazol-5-ol (Molidustat)==
-	<StructureSection load='6zbo' size='340' side='right'caption='[[6zbo]]' scene=''>	+	<StructureSection load='6zbo' size='340' side='right'caption='[[6zbo]], [[Resolution\|resolution]] 1.79Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZBO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZBO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6zbo]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZBO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZBO FirstGlance]. <br>
-	</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=6zbo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zbo OCA], [https://pdbe.org/6zbo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zbo RCSB], [https://www.ebi.ac.uk/pdbsum/6zbo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zbo ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=QEQ:2-(6-morpholin-4-ylpyrimidin-4-yl)-4-(1,2,3-triazol-1-yl)pyrazol-3-ol'>QEQ</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EGLN1, C1orf12, PNAS-118, PNAS-137 ([https://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'>[https://en.wikipedia.org/wiki/Hypoxia-inducible_factor-proline_dioxygenase Hypoxia-inducible factor-proline dioxygenase], with EC number [https://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=6zbo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zbo OCA], [https://pdbe.org/6zbo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zbo RCSB], [https://www.ebi.ac.uk/pdbsum/6zbo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zbo ProSAT]</span></td></tr>
	</table>		</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 ==
		+	Human prolyl-hydroxylases (PHDs) are hypoxia-sensing 2-oxoglutarate (2OG) oxygenases, catalysis by which suppresses the transcription of hypoxia-inducible factor target genes. PHD inhibition enables the treatment of anaemia/ischaemia-related disease. The PHD inhibitor Molidustat is approved for the treatment of renal anaemia; it differs from other approved/late-stage PHD inhibitors in lacking a glycinamide side chain. The first reported crystal structures of Molidustat and IOX4 (a brain-penetrating derivative) complexed with PHD2 reveal how their contiguous triazole, pyrazolone and pyrimidine/pyridine rings bind at the active site. The inhibitors bind to the active-site metal in a bidentate manner through their pyrazolone and pyrimidine nitrogens, with the triazole pi-pi-stacking with Tyr303 in the 2OG binding pocket. Comparison of the new structures with other PHD inhibitor complexes reveals differences in the conformations of Tyr303, Tyr310, and a mobile loop linking beta2-beta3, which are involved in dynamic substrate binding/product release.
		+
		+	Structural Basis of Prolyl Hydroxylase Domain Inhibition by Molidustat.,Figg WD Jr, McDonough MA, Chowdhury R, Nakashima Y, Zhang Z, Holt-Martyn JP, Krajnc A, Schofield CJ ChemMedChem. 2021 Jul 6;16(13):2082-2088. doi: 10.1002/cmdc.202100133. Epub 2021 , Apr 9. PMID:33792169<ref>PMID:33792169</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6zbo" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Hypoxia-inducible factor-proline dioxygenase]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Figg Jr WD~~]]	+	[[Category: Holt-Martyn, J P]]
-	[[Category: ~~Holt-Martyn JP~~]]	+	[[Category: Jr, W D.Figg]]
-	[[Category: McDonough MA]]	+	[[Category: McDonough, M A]]
-	[[Category: Nakashima Y]]	+	[[Category: Nakashima, Y]]
-	[[Category: Schofield CJ]]	+	[[Category: Schofield, C J]]
		+	[[Category: Complex]]
		+	[[Category: Hif]]
		+	[[Category: Inhibitor]]
		+	[[Category: Molidustat]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Phd2]]

OCA at 06:46, 7 April 2021

OCA — Wed, 07 Apr 2021 06:46:41 GMT

←Older revision		Revision as of 06:46, 7 April 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 6zbo is ~~ON HOLD until Paper Publication~~	+	==HIF Prolyl Hydroxylase 2 (PHD2/EGLN1) in Complex with 1-(6-morpholinopyrimidin-4-yl)-4-(1H-1,2,3-triazol-1-yl)-1H-pyrazol-5-ol (Molidustat)==
-		+	<StructureSection load='6zbo' size='340' side='right'caption='[[6zbo]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZBO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZBO FirstGlance]. <br>
-	~~Description~~:	+	</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=6zbo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zbo OCA], [https://pdbe.org/6zbo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zbo RCSB], [https://www.ebi.ac.uk/pdbsum/6zbo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zbo ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Figg Jr WD]]
		+	[[Category: Holt-Martyn JP]]
		+	[[Category: McDonough MA]]
		+	[[Category: Nakashima Y]]
		+	[[Category: Schofield CJ]]

OCA at 14:23, 10 March 2021

OCA — Wed, 10 Mar 2021 14:23:28 GMT

←Older revision		Revision as of 14:23, 10 March 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6zbo is ON HOLD	+	The entry 6zbo is ON HOLD until Paper Publication

	Authors:		Authors:

OCA at 13:05, 3 March 2021

OCA — Wed, 03 Mar 2021 13:05:29 GMT

←Older revision		Revision as of 13:05, 3 March 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6zbo is ON HOLD ~~until Paper Publication~~	+	The entry 6zbo is ON HOLD

	Authors:		Authors:

OCA at 11:04, 8 July 2020

OCA — Wed, 08 Jul 2020 11:04:08 GMT

←Older revision		Revision as of 11:04, 8 July 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6zbo is ON HOLD	+	The entry 6zbo is ON HOLD until Paper Publication

	Authors:		Authors:

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

OCA — Wed, 17 Jun 2020 08:54:25 GMT

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

←Older revision

Revision as of 08:54, 17 June 2020

OCA: New page: '''Unreleased structure''' The entry 6zbo is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 17 Jun 2020 08:54:23 GMT

New page: '''Unreleased structure''' The entry 6zbo is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6zbo is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]