5op6 - Revision history

OCA at 16:57, 13 December 2023

OCA — Wed, 13 Dec 2023 16:57:14 GMT

←Older revision		Revision as of 16:57, 13 December 2023
Line 1:		Line 1:

	==Factor Inhibiting HIF (FIH) in complex with zinc and GSK128863==		==Factor Inhibiting HIF (FIH) in complex with zinc and GSK128863==
-	<StructureSection load='5op6' size='340' side='right' caption='[[5op6]], [[Resolution\|resolution]] 2.45Å' scene=''>	+	<StructureSection load='5op6' size='340' side='right'caption='[[5op6]], [[Resolution\|resolution]] 2.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5op6]] 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=5OP6 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5OP6 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5op6]] 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=5OP6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OP6 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A0W:2-[[1,3-dicyclohexyl-4-oxidanyl-2,6-bis(oxidanylidene)pyrimidin-5-yl]carbonylamino]ethanoic+acid'>A0W</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.45Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HIF1AN, FIH1 ([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=A0W:2-[[1,3-dicyclohexyl-4-oxidanyl-2,6-bis(oxidanylidene)pyrimidin-5-yl]carbonylamino]ethanoic+acid'>A0W</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=5op6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5op6 OCA], [~~http~~://pdbe.org/5op6 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5op6 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5op6 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5op6 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=5op6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5op6 OCA], [https://pdbe.org/5op6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5op6 RCSB], [https://www.ebi.ac.uk/pdbsum/5op6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5op6 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/HIF1N_HUMAN HIF1N_HUMAN]] Hydroxylates HIF-1 alpha at 'Asp-803' in the C-terminal transactivation domain (CAD). Functions as an oxygen sensor and, under normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300-interacting transactivator. Involved in transcriptional repression through interaction with HIF1A, VHL and histone deacetylases. Hydroxylates specific Asn residues within ankyrin repeat domains (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A and several other ARD-containing proteins. Also hydroxylates Asp and His residues within ARDs of ANK1 and TNKS2, respectively. Negatively regulates NOTCH1 activity, accelerating myogenic differentiation. Positively regulates ASB4 activity, promoting vascular differentiation.<ref>PMID:12080085</ref> <ref>PMID:12042299</ref> <ref>PMID:17003112</ref> <ref>PMID:18299578</ref> <ref>PMID:19245366</ref> <ref>PMID:17573339</ref> <ref>PMID:21251231</ref> <ref>PMID:21177872</ref>	+	[https://www.uniprot.org/uniprot/HIF1N_HUMAN HIF1N_HUMAN] Hydroxylates HIF-1 alpha at 'Asp-803' in the C-terminal transactivation domain (CAD). Functions as an oxygen sensor and, under normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300-interacting transactivator. Involved in transcriptional repression through interaction with HIF1A, VHL and histone deacetylases. Hydroxylates specific Asn residues within ankyrin repeat domains (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A and several other ARD-containing proteins. Also hydroxylates Asp and His residues within ARDs of ANK1 and TNKS2, respectively. Negatively regulates NOTCH1 activity, accelerating myogenic differentiation. Positively regulates ASB4 activity, promoting vascular differentiation.<ref>PMID:12080085</ref> <ref>PMID:12042299</ref> <ref>PMID:17003112</ref> <ref>PMID:18299578</ref> <ref>PMID:19245366</ref> <ref>PMID:17573339</ref> <ref>PMID:21251231</ref> <ref>PMID:21177872</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5op6" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5op6" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Factor inhibiting HIF\|Factor inhibiting HIF]]
		+	*[[Hypoxia-Inducible factor 1 alpha inhibitor\|Hypoxia-Inducible factor 1 alpha inhibitor]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Clifton, I J~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Leissing, T M~~]]	+	[[Category: Clifton IJ]]
-	[[Category: ~~Lu, X~~]]	+	[[Category: Leissing TM]]
-	[[Category: ~~Schofield, C J~~]]	+	[[Category: Lu X]]
-	[[Category: ~~Thinnes, C C~~]]	+	[[Category: Schofield CJ]]
-	[[Category: ~~Activator-inhibitor]]~~	+	[[Category: Thinnes CC]]
-	~~[[Category: Ard]]~~	+
-	~~[[Category: Asparaginyl/aspartyl hydroxylase]]~~	+
-	~~[[Category: Beta-hydroxylation]]~~	+
-	~~[[Category: Dioxygenase]]~~	+
-	~~[[Category: Dna-binding]]~~	+
-	~~[[Category: Dsbh]]~~	+
-	~~[[Category: Epigenetic regulation]]~~	+
-	~~[[Category: Facial triad]]~~	+
-	~~[[Category: Helix-loop-helix-beta]]~~	+
-	~~[[Category: Metal-binding]]~~	+
-	~~[[Category: On-heme]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Oxidoreductase-peptide complex]]~~	+
-	~~[[Category: Oxygenase]]~~	+
-	~~[[Category: Signaling]]~~	+
-	~~[[Category: Transcription~~]]	+

OCA at 07:46, 22 February 2018

OCA — Thu, 22 Feb 2018 07:46:36 GMT

←Older revision		Revision as of 07:46, 22 February 2018
Line 3:		Line 3:
	<StructureSection load='5op6' size='340' side='right' caption='[[5op6]], [[Resolution\|resolution]] 2.45Å' scene=''>		<StructureSection load='5op6' size='340' side='right' caption='[[5op6]], [[Resolution\|resolution]] 2.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5op6]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OP6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OP6 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5op6]] 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=5OP6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OP6 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A0W:2-[[1,3-dicyclohexyl-4-oxidanyl-2,6-bis(oxidanylidene)pyrimidin-5-yl]carbonylamino]ethanoic+acid'>A0W</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A0W:2-[[1,3-dicyclohexyl-4-oxidanyl-2,6-bis(oxidanylidene)pyrimidin-5-yl]carbonylamino]ethanoic+acid'>A0W</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HIF1AN, FIH1 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5op6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5op6 OCA], [http://pdbe.org/5op6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5op6 RCSB], [http://www.ebi.ac.uk/pdbsum/5op6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5op6 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=5op6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5op6 OCA], [http://pdbe.org/5op6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5op6 RCSB], [http://www.ebi.ac.uk/pdbsum/5op6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5op6 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/HIF1N_HUMAN HIF1N_HUMAN]] Hydroxylates HIF-1 alpha at 'Asp-803' in the C-terminal transactivation domain (CAD). Functions as an oxygen sensor and, under normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300-interacting transactivator. Involved in transcriptional repression through interaction with HIF1A, VHL and histone deacetylases. Hydroxylates specific Asn residues within ankyrin repeat domains (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A and several other ARD-containing proteins. Also hydroxylates Asp and His residues within ARDs of ANK1 and TNKS2, respectively. Negatively regulates NOTCH1 activity, accelerating myogenic differentiation. Positively regulates ASB4 activity, promoting vascular differentiation.<ref>PMID:12080085</ref> <ref>PMID:12042299</ref> <ref>PMID:17003112</ref> <ref>PMID:18299578</ref> <ref>PMID:19245366</ref> <ref>PMID:17573339</ref> <ref>PMID:21251231</ref> <ref>PMID:21177872</ref>		[[http://www.uniprot.org/uniprot/HIF1N_HUMAN HIF1N_HUMAN]] Hydroxylates HIF-1 alpha at 'Asp-803' in the C-terminal transactivation domain (CAD). Functions as an oxygen sensor and, under normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300-interacting transactivator. Involved in transcriptional repression through interaction with HIF1A, VHL and histone deacetylases. Hydroxylates specific Asn residues within ankyrin repeat domains (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A and several other ARD-containing proteins. Also hydroxylates Asp and His residues within ARDs of ANK1 and TNKS2, respectively. Negatively regulates NOTCH1 activity, accelerating myogenic differentiation. Positively regulates ASB4 activity, promoting vascular differentiation.<ref>PMID:12080085</ref> <ref>PMID:12042299</ref> <ref>PMID:17003112</ref> <ref>PMID:18299578</ref> <ref>PMID:19245366</ref> <ref>PMID:17573339</ref> <ref>PMID:21251231</ref> <ref>PMID:21177872</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Inhibition of the human 2-oxoglutarate (2OG) dependent hypoxia inducible factor (HIF) prolyl hydroxylases (human PHD1-3) causes upregulation of HIF, thus promoting erythropoiesis and is therefore of therapeutic interest. We describe cellular, biophysical, and biochemical studies comparing four PHD inhibitors currently in clinical trials for anaemia treatment, that describe their mechanisms of action, potency against isolated enzymes and in cells, and selectivities versus representatives of other human 2OG oxygenase subfamilies. The 'clinical' PHD inhibitors are potent inhibitors of PHD catalyzed hydroxylation of the HIF-alpha oxygen dependent degradation domains (ODDs), and selective against most, but not all, representatives of other human 2OG dependent dioxygenase subfamilies. Crystallographic and NMR studies provide insights into the different active site binding modes of the inhibitors. Cell-based results reveal the inhibitors have similar effects on the upregulation of HIF target genes, but differ in the kinetics of their effects and in extent of inhibition of hydroxylation of the N- and C-terminal ODDs; the latter differences correlate with the biophysical observations.
		+
		+	Molecular and cellular mechanisms of HIF prolyl hydroxylase inhibitors in clinical trials.,Yeh TL, Leissing TM, Abboud MI, Thinnes CC, Atasoylu O, Holt-Martyn JP, Zhang D, Tumber A, Lippl K, Lohans CT, Leung IKH, Morcrette H, Clifton IJ, Claridge TDW, Kawamura A, Flashman E, Lu X, Ratcliffe PJ, Chowdhury R, Pugh CW, Schofield CJ Chem Sci. 2017 Nov 1;8(11):7651-7668. doi: 10.1039/c7sc02103h. Epub 2017 Sep 11. PMID:29435217<ref>PMID:29435217</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5op6" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Clifton, I J]]		[[Category: Clifton, I J]]
	[[Category: Leissing, T M]]		[[Category: Leissing, T M]]

OCA at 07:12, 18 October 2017

OCA — Wed, 18 Oct 2017 07:12:55 GMT

←Older revision		Revision as of 07:12, 18 October 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5op6 is ~~ON HOLD~~ ~~until Paper Publication~~	+	==Factor Inhibiting HIF (FIH) in complex with zinc and GSK128863==
-		+	<StructureSection load='5op6' size='340' side='right' caption='[[5op6]], [[Resolution\|resolution]] 2.45Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5op6]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OP6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OP6 FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A0W:2-[[1,3-dicyclohexyl-4-oxidanyl-2,6-bis(oxidanylidene)pyrimidin-5-yl]carbonylamino]ethanoic+acid'>A0W</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<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=5op6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5op6 OCA], [http://pdbe.org/5op6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5op6 RCSB], [http://www.ebi.ac.uk/pdbsum/5op6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5op6 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/HIF1N_HUMAN HIF1N_HUMAN]] Hydroxylates HIF-1 alpha at 'Asp-803' in the C-terminal transactivation domain (CAD). Functions as an oxygen sensor and, under normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300-interacting transactivator. Involved in transcriptional repression through interaction with HIF1A, VHL and histone deacetylases. Hydroxylates specific Asn residues within ankyrin repeat domains (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A and several other ARD-containing proteins. Also hydroxylates Asp and His residues within ARDs of ANK1 and TNKS2, respectively. Negatively regulates NOTCH1 activity, accelerating myogenic differentiation. Positively regulates ASB4 activity, promoting vascular differentiation.<ref>PMID:12080085</ref> <ref>PMID:12042299</ref> <ref>PMID:17003112</ref> <ref>PMID:18299578</ref> <ref>PMID:19245366</ref> <ref>PMID:17573339</ref> <ref>PMID:21251231</ref> <ref>PMID:21177872</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Clifton, I J]]
		+	[[Category: Leissing, T M]]
		+	[[Category: Lu, X]]
		+	[[Category: Schofield, C J]]
		+	[[Category: Thinnes, C C]]
		+	[[Category: Activator-inhibitor]]
		+	[[Category: Ard]]
		+	[[Category: Asparaginyl/aspartyl hydroxylase]]
		+	[[Category: Beta-hydroxylation]]
		+	[[Category: Dioxygenase]]
		+	[[Category: Dna-binding]]
		+	[[Category: Dsbh]]
		+	[[Category: Epigenetic regulation]]
		+	[[Category: Facial triad]]
		+	[[Category: Helix-loop-helix-beta]]
		+	[[Category: Metal-binding]]
		+	[[Category: On-heme]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Oxidoreductase-peptide complex]]
		+	[[Category: Oxygenase]]
		+	[[Category: Signaling]]
		+	[[Category: Transcription]]

OCA: Protected "5op6" [edit=sysop:move=sysop]

OCA — Wed, 27 Sep 2017 12:40:26 GMT

Protected "5op6" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:40, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5op6 is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

OCA — Wed, 27 Sep 2017 12:40:25 GMT

New page: '''Unreleased structure''' The entry 5op6 is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5op6 is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]