4h6j - Revision history

OCA at 11:35, 1 March 2024

OCA — Fri, 01 Mar 2024 11:35:46 GMT

←Older revision		Revision as of 11:35, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4h6j]] is a 2 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=4H6J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4H6J FirstGlance]. <br>		<table><tr><td colspan='2'>[[4h6j]] is a 2 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=4H6J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4H6J 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=4h6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h6j OCA], [https://pdbe.org/4h6j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4h6j RCSB], [https://www.ebi.ac.uk/pdbsum/4h6j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4h6j ProSAT]</span></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]] 1.52Å</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=4h6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h6j OCA], [https://pdbe.org/4h6j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4h6j RCSB], [https://www.ebi.ac.uk/pdbsum/4h6j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4h6j ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/HIF1A_HUMAN HIF1A_HUMAN] Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBPB and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia.<ref>PMID:9887100</ref> <ref>PMID:11566883</ref> <ref>PMID:11292861</ref> <ref>PMID:15465032</ref> <ref>PMID:16543236</ref> <ref>PMID:16973622</ref> <ref>PMID:17610843</ref> <ref>PMID:19528298</ref> <ref>PMID:20624928</ref>		[https://www.uniprot.org/uniprot/HIF1A_HUMAN HIF1A_HUMAN] Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBPB and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia.<ref>PMID:9887100</ref> <ref>PMID:11566883</ref> <ref>PMID:11292861</ref> <ref>PMID:15465032</ref> <ref>PMID:16543236</ref> <ref>PMID:16973622</ref> <ref>PMID:17610843</ref> <ref>PMID:19528298</ref> <ref>PMID:20624928</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The heterodimer HIF-1alpha (hypoxia inducible factor)/HIF-beta (also known as ARNT-aryl hydrocarbon nuclear translocator) is a key mediator of cellular response to hypoxia. The interaction between these monomer units can be modified by the action of small molecules in the binding interface between their C-terminal heterodimerization (PasB) domains. Taking advantage of the presence of several cysteine residues located in the allosteric cavity of HIF-1alpha PasB domain, we applied a cysteine-based reactomics "hotspot identification" strategy to locate regions of HIF-1alpha PasB domain critical for its interaction with ARNT. COMPOUND 5 was identified using a mass spectrometry-based primary screening strategy and was shown to react specifically with Cys255 of the HIF-1alpha PasB domain. Biophysical characterization of the interaction between PasB domains of HIF-1alpha and ARNT revealed that covalent binding of COMPOUND 5 to Cys255 reduced binding affinity between HIF-1alpha and ARNT PasB domains approximately 10-fold. Detailed NMR structural analysis of HIF-1alpha-PasB-COMPOUND 5 conjugate showed significant local conformation changes in the HIF-1alpha associated with key residues involved in the HIF-1alpha/ARNT PasB domain interaction as revealed by the crystal structure of the HIF-1alpha/ARNT PasB heterodimer. Our screening strategy could be applied to other targets to identify pockets surrounding reactive cysteines suitable for development of small molecule modulators of protein function.
-
-	Identification of Cys255 in HIF-1alpha as a novel site for development of covalent inhibitors of HIF-1alpha/ARNT PasB domain protein-protein interaction.,Cardoso R, Love R, Nilsson CL, Bergqvist S, Nowlin D, Yan J, Liu KK, Zhu J, Chen P, Deng YL, Dyson HJ, Greig MJ, Brooun A Protein Sci. 2012 Dec;21(12):1885-96. doi: 10.1002/pro.2172. Epub 2012 Nov 9. PMID:23033253<ref>PMID:23033253</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4h6j" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 08:02, 3 November 2022

OCA — Thu, 03 Nov 2022 08:02:14 GMT

←Older revision		Revision as of 08:02, 3 November 2022
Line 1:		Line 1:

	==Identification of Cys 255 in HIF-1 as a novel site for development of covalent inhibitors of HIF-1 /ARNT PasB domain protein-protein interaction.==		==Identification of Cys 255 in HIF-1 as a novel site for development of covalent inhibitors of HIF-1 /ARNT PasB domain protein-protein interaction.==
-	<StructureSection load='4h6j' size='340' side='right' caption='[[4h6j]], [[Resolution\|resolution]] 1.52Å' scene=''>	+	<StructureSection load='4h6j' size='340' side='right'caption='[[4h6j]], [[Resolution\|resolution]] 1.52Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4h6j]] is a 2 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=4H6J OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4H6J FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4h6j]] is a 2 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=4H6J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4H6J FirstGlance]. <br>
-	</td></tr>~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3f1p\|3f1p]]</td></tr>~~	+	</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=4h6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h6j OCA], [https://pdbe.org/4h6j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4h6j RCSB], [https://www.ebi.ac.uk/pdbsum/4h6j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4h6j ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HIF-1 alpha ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ARNT ([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=4h6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h6j OCA], [~~http~~://pdbe.org/4h6j PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4h6j RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4h6j PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4h6j ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/HIF1A_HUMAN HIF1A_HUMAN]] Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBPB and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia.<ref>PMID:9887100</ref> <ref>PMID:11566883</ref> <ref>PMID:11292861</ref> <ref>PMID:15465032</ref> <ref>PMID:16543236</ref> <ref>PMID:16973622</ref> <ref>PMID:17610843</ref> <ref>PMID:19528298</ref> <ref>PMID:20624928</ref> [[http://www.uniprot.org/uniprot/ARNT_HUMAN ARNT_HUMAN]] Required for activity of the Ah (dioxin) receptor. This protein is required for the ligand-binding subunit to translocate from the cytosol to the nucleus after ligand binding. The complex then initiates transcription of genes involved in the activation of PAH procarcinogens. The heterodimer with HIF1A or EPAS1/HIF2A functions as a transcriptional regulator of the adaptive response to hypoxia.	+	[https://www.uniprot.org/uniprot/HIF1A_HUMAN HIF1A_HUMAN] Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBPB and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia.<ref>PMID:9887100</ref> <ref>PMID:11566883</ref> <ref>PMID:11292861</ref> <ref>PMID:15465032</ref> <ref>PMID:16543236</ref> <ref>PMID:16973622</ref> <ref>PMID:17610843</ref> <ref>PMID:19528298</ref> <ref>PMID:20624928</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 19:		Line 17:
	</div>		</div>
	<div class="pdbe-citations 4h6j" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4h6j" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Factor inhibiting HIF\|Factor inhibiting HIF]]
		+	*[[3D structures of hypoxia-inducible factor\|3D structures of hypoxia-inducible factor]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: Bergqvist, S]]	+	[[Category: Large Structures]]
-	[[Category: Brooun, A]]	+	[[Category: Bergqvist S]]
-	[[Category: Cardoso, R]]	+	[[Category: Brooun A]]
-	[[Category: Chen, P]]	+	[[Category: Cardoso R]]
-	[[Category: Deng, Y L]]	+	[[Category: Chen P]]
-	[[Category: Dyson~~, H J~~]]	+	[[Category: Deng Y-L]]
-	[[Category: Greig~~, M J~~]]	+	[[Category: Dyson HJ]]
-	[[Category: Liu, K]]	+	[[Category: Greig MJ]]
-	[[Category: Love~~, R A~~]]	+	[[Category: Liu K]]
-	[[Category: Nilsson, C]]	+	[[Category: Love RA]]
-	[[Category: Nowlin, D]]	+	[[Category: Nilsson C]]
-	[[Category: Yan, J]]	+	[[Category: Nowlin D]]
-	[[Category: Zhu, J]]	+	[[Category: Yan J]]
-	~~[[Category: Arnt]]~~	+	[[Category: Zhu J]]
-	~~[[Category: Heterodimer]]~~	+
-	~~[[Category: Hypoxia inducible factor]]~~	+
-	~~[[Category: Pas domain]]~~	+
-	~~[[Category: Transcription]]~~	+
-	~~[[Category: Transcription factor~~]]	+

OCA at 19:59, 24 January 2018

OCA — Wed, 24 Jan 2018 19:59:18 GMT

←Older revision		Revision as of 19:59, 24 January 2018
Line 1:		Line 1:
		+
	==Identification of Cys 255 in HIF-1 as a novel site for development of covalent inhibitors of HIF-1 /ARNT PasB domain protein-protein interaction.==		==Identification of Cys 255 in HIF-1 as a novel site for development of covalent inhibitors of HIF-1 /ARNT PasB domain protein-protein interaction.==
	<StructureSection load='4h6j' size='340' side='right' caption='[[4h6j]], [[Resolution\|resolution]] 1.52Å' scene=''>		<StructureSection load='4h6j' size='340' side='right' caption='[[4h6j]], [[Resolution\|resolution]] 1.52Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4h6j]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4H6J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4H6J FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4h6j]] is a 2 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=4H6J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4H6J FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3f1p\|3f1p]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3f1p\|3f1p]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HIF-1 alpha ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~]), ARNT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HIF-1 alpha ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ARNT ([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=4h6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h6j OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4h6j RCSB], [http://www.ebi.ac.uk/pdbsum/4h6j PDBsum]</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=4h6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h6j OCA], [http://pdbe.org/4h6j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4h6j RCSB], [http://www.ebi.ac.uk/pdbsum/4h6j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4h6j ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 18:
	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>
	</div>		</div>
-		+	<div class="pdbe-citations 4h6j" style="background-color:#fffaf0;"></div>
-	==~~See Also==~~	+
-	*[[Factor inhibiting HIF\|Factor inhibiting HIF]]	+
-	*[[Hypoxia-inducible factor prolyl hydroxylase\|Hypoxia-~~inducible factor prolyl hydroxylase]]~~	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Bergqvist, S]]		[[Category: Bergqvist, S]]
	[[Category: Brooun, A]]		[[Category: Brooun, A]]

OCA at 06:05, 25 December 2014

OCA — Thu, 25 Dec 2014 06:05:16 GMT

←Older revision		Revision as of 06:05, 25 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4h6j\| PDB=4h6j \| SCENE= }}~~	+	==Identification of Cys 255 in HIF-1 as a novel site for development of covalent inhibitors of HIF-1 /ARNT PasB domain protein-protein interaction.==
-	===Identification of Cys 255 in HIF-1 as a novel site for development of covalent inhibitors of HIF-1 /ARNT PasB domain protein-protein interaction.===	+	<StructureSection load='4h6j' size='340' side='right' caption='[[4h6j]], [[Resolution\|resolution]] 1.52Å' scene=''>
-	~~{{ABSTRACT_PUBMED_23033253}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4h6j]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4H6J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4H6J FirstGlance]. <br>
-	==Function==	+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3f1p\|3f1p]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HIF-1 alpha ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), ARNT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4h6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h6j OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4h6j RCSB], [http://www.ebi.ac.uk/pdbsum/4h6j PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
	[[http://www.uniprot.org/uniprot/HIF1A_HUMAN HIF1A_HUMAN]] Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBPB and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia.<ref>PMID:9887100</ref> <ref>PMID:11566883</ref> <ref>PMID:11292861</ref> <ref>PMID:15465032</ref> <ref>PMID:16543236</ref> <ref>PMID:16973622</ref> <ref>PMID:17610843</ref> <ref>PMID:19528298</ref> <ref>PMID:20624928</ref> [[http://www.uniprot.org/uniprot/ARNT_HUMAN ARNT_HUMAN]] Required for activity of the Ah (dioxin) receptor. This protein is required for the ligand-binding subunit to translocate from the cytosol to the nucleus after ligand binding. The complex then initiates transcription of genes involved in the activation of PAH procarcinogens. The heterodimer with HIF1A or EPAS1/HIF2A functions as a transcriptional regulator of the adaptive response to hypoxia.		[[http://www.uniprot.org/uniprot/HIF1A_HUMAN HIF1A_HUMAN]] Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBPB and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia.<ref>PMID:9887100</ref> <ref>PMID:11566883</ref> <ref>PMID:11292861</ref> <ref>PMID:15465032</ref> <ref>PMID:16543236</ref> <ref>PMID:16973622</ref> <ref>PMID:17610843</ref> <ref>PMID:19528298</ref> <ref>PMID:20624928</ref> [[http://www.uniprot.org/uniprot/ARNT_HUMAN ARNT_HUMAN]] Required for activity of the Ah (dioxin) receptor. This protein is required for the ligand-binding subunit to translocate from the cytosol to the nucleus after ligand binding. The complex then initiates transcription of genes involved in the activation of PAH procarcinogens. The heterodimer with HIF1A or EPAS1/HIF2A functions as a transcriptional regulator of the adaptive response to hypoxia.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The heterodimer HIF-1alpha (hypoxia inducible factor)/HIF-beta (also known as ARNT-aryl hydrocarbon nuclear translocator) is a key mediator of cellular response to hypoxia. The interaction between these monomer units can be modified by the action of small molecules in the binding interface between their C-terminal heterodimerization (PasB) domains. Taking advantage of the presence of several cysteine residues located in the allosteric cavity of HIF-1alpha PasB domain, we applied a cysteine-based reactomics "hotspot identification" strategy to locate regions of HIF-1alpha PasB domain critical for its interaction with ARNT. COMPOUND 5 was identified using a mass spectrometry-based primary screening strategy and was shown to react specifically with Cys255 of the HIF-1alpha PasB domain. Biophysical characterization of the interaction between PasB domains of HIF-1alpha and ARNT revealed that covalent binding of COMPOUND 5 to Cys255 reduced binding affinity between HIF-1alpha and ARNT PasB domains approximately 10-fold. Detailed NMR structural analysis of HIF-1alpha-PasB-COMPOUND 5 conjugate showed significant local conformation changes in the HIF-1alpha associated with key residues involved in the HIF-1alpha/ARNT PasB domain interaction as revealed by the crystal structure of the HIF-1alpha/ARNT PasB heterodimer. Our screening strategy could be applied to other targets to identify pockets surrounding reactive cysteines suitable for development of small molecule modulators of protein function.

-	~~==About this Structure==~~	+	Identification of Cys255 in HIF-1alpha as a novel site for development of covalent inhibitors of HIF-1alpha/ARNT PasB domain protein-protein interaction.,Cardoso R, Love R, Nilsson CL, Bergqvist S, Nowlin D, Yan J, Liu KK, Zhu J, Chen P, Deng YL, Dyson HJ, Greig MJ, Brooun A Protein Sci. 2012 Dec;21(12):1885-96. doi: 10.1002/pro.2172. Epub 2012 Nov 9. PMID:23033253<ref>PMID:23033253</ref>
-	~~[[4h6j]] is~~ a ~~2 chain structure with sequence from [http:/~~/en.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http~~:/~~/oca~~.~~weizmann~~.ac.il/~~oca-bin~~/~~ocashort?id=4H6J OCA]~~.	+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

	==See Also==		==See Also==
		+	*[[Factor inhibiting HIF\|Factor inhibiting HIF]]
	*[[Hypoxia-inducible factor prolyl hydroxylase\|Hypoxia-inducible factor prolyl hydroxylase]]		*[[Hypoxia-inducible factor prolyl hydroxylase\|Hypoxia-inducible factor prolyl hydroxylase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:023033253</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Bergqvist, S.]]	+	[[Category: Bergqvist, S]]
-	[[Category: Brooun, A.]]	+	[[Category: Brooun, A]]
-	[[Category: Cardoso, R.]]	+	[[Category: Cardoso, R]]
-	[[Category: Chen, P.]]	+	[[Category: Chen, P]]
-	[[Category: Deng, Y L.]]	+	[[Category: Deng, Y L]]
-	[[Category: Dyson, H J.]]	+	[[Category: Dyson, H J]]
-	[[Category: Greig, M J.]]	+	[[Category: Greig, M J]]
-	[[Category: Liu, K.]]	+	[[Category: Liu, K]]
-	[[Category: Love, R A.]]	+	[[Category: Love, R A]]
-	[[Category: Nilsson, C.]]	+	[[Category: Nilsson, C]]
-	[[Category: Nowlin, D.]]	+	[[Category: Nowlin, D]]
-	[[Category: Yan, J.]]	+	[[Category: Yan, J]]
	[[Category: Zhu, J]]		[[Category: Zhu, J]]
	[[Category: Arnt]]		[[Category: Arnt]]

OCA at 05:00, 28 August 2013

OCA — Wed, 28 Aug 2013 05:00:23 GMT

←Older revision		Revision as of 05:00, 28 August 2013
Line 1:		Line 1:
-	[[Image:4h6j.jpg\|left\|200px]]
-
	{{STRUCTURE_4h6j\| PDB=4h6j \| SCENE= }}		{{STRUCTURE_4h6j\| PDB=4h6j \| SCENE= }}
-
	===Identification of Cys 255 in HIF-1 as a novel site for development of covalent inhibitors of HIF-1 /ARNT PasB domain protein-protein interaction.===		===Identification of Cys 255 in HIF-1 as a novel site for development of covalent inhibitors of HIF-1 /ARNT PasB domain protein-protein interaction.===
		+	{{ABSTRACT_PUBMED_23033253}}

		+	==Function==
		+	[[http://www.uniprot.org/uniprot/HIF1A_HUMAN HIF1A_HUMAN]] Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBPB and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia.<ref>PMID:9887100</ref> <ref>PMID:11566883</ref> <ref>PMID:11292861</ref> <ref>PMID:15465032</ref> <ref>PMID:16543236</ref> <ref>PMID:16973622</ref> <ref>PMID:17610843</ref> <ref>PMID:19528298</ref> <ref>PMID:20624928</ref> [[http://www.uniprot.org/uniprot/ARNT_HUMAN ARNT_HUMAN]] Required for activity of the Ah (dioxin) receptor. This protein is required for the ligand-binding subunit to translocate from the cytosol to the nucleus after ligand binding. The complex then initiates transcription of genes involved in the activation of PAH procarcinogens. The heterodimer with HIF1A or EPAS1/HIF2A functions as a transcriptional regulator of the adaptive response to hypoxia.

	==About this Structure==		==About this Structure==
	[[4h6j]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4H6J OCA].		[[4h6j]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4H6J OCA].
		+
		+	==See Also==
		+	*[[Hypoxia-inducible factor prolyl hydroxylase\|Hypoxia-inducible factor prolyl hydroxylase]]
		+
		+	==Reference==
		+	<ref group="xtra">PMID:023033253</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Bergqvist, S.]]		[[Category: Bergqvist, S.]]

OCA at 11:01, 5 December 2012

OCA — Wed, 05 Dec 2012 11:01:18 GMT

←Older revision		Revision as of 11:01, 5 December 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4h6j.jpg\|left\|200px]]

-	~~The entry~~ 4h6j ~~is ON HOLD~~	+	{{STRUCTURE_4h6j\| PDB=4h6j \| SCENE= }}

-	~~Authors: Cardoso, R., Love, R.A., Nilsson, C., Bergqvist, S., Nowlin, D., Yan, J., Liu, K., Zhu, J, Chen, P., Deng, Y.~~-~~L., Dyson, H.J., Greig, M.J., Brooun, A~~.	+	===Identification of Cys 255 in HIF-1 as a novel site for development of covalent inhibitors of HIF-1 /ARNT PasB domain protein-protein interaction.===

-	~~Description: Identification of Cys 255 in HIF-1 as~~ a ~~novel site for development of covalent inhibitors of HIF-1~~ /~~ARNT PasB domain protein~~-~~protein interaction~~.	+
		+	==About this Structure==
		+	[[4h6j]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4H6J OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Bergqvist, S.]]
		+	[[Category: Brooun, A.]]
		+	[[Category: Cardoso, R.]]
		+	[[Category: Chen, P.]]
		+	[[Category: Deng, Y L.]]
		+	[[Category: Dyson, H J.]]
		+	[[Category: Greig, M J.]]
		+	[[Category: Liu, K.]]
		+	[[Category: Love, R A.]]
		+	[[Category: Nilsson, C.]]
		+	[[Category: Nowlin, D.]]
		+	[[Category: Yan, J.]]
		+	[[Category: Zhu, J]]
		+	[[Category: Arnt]]
		+	[[Category: Heterodimer]]
		+	[[Category: Hypoxia inducible factor]]
		+	[[Category: Pas domain]]
		+	[[Category: Transcription]]
		+	[[Category: Transcription factor]]

OCA at 06:56, 10 October 2012

OCA — Wed, 10 Oct 2012 06:56:37 GMT

←Older revision		Revision as of 06:56, 10 October 2012
Line 3:		Line 3:
	The entry 4h6j is ON HOLD		The entry 4h6j is ON HOLD

-	Authors: Cardoso, R., Love, R.A., Nilsson, C., Bergqvist, S., Nowlin, D., Yan, ~~Jiangli~~, Liu, K., Zhu, J, Chen, P., Deng, Y.-L., Dyson, H.J., Greig, M.J., Brooun, A.	+	Authors: Cardoso, R., Love, R.A., Nilsson, C., Bergqvist, S., Nowlin, D., Yan, J., Liu, K., Zhu, J, Chen, P., Deng, Y.-L., Dyson, H.J., Greig, M.J., Brooun, A.

	Description: Identification of Cys 255 in HIF-1 as a novel site for development of covalent inhibitors of HIF-1 /ARNT PasB domain protein-protein interaction.		Description: Identification of Cys 255 in HIF-1 as a novel site for development of covalent inhibitors of HIF-1 /ARNT PasB domain protein-protein interaction.

OCA: Protected "4h6j" [edit=sysop:move=sysop]

OCA — Wed, 26 Sep 2012 20:14:14 GMT

Protected "4h6j" [edit=sysop:move=sysop]

←Older revision

Revision as of 20:14, 26 September 2012

OCA: New page: '''Unreleased structure''' The entry 4h6j is ON HOLD Authors: Cardoso, R., Love, R.A., Nilsson, C., Bergqvist, S., Nowlin, D., Yan, Jiangli, Liu, K., Zhu, J, Chen, P., Deng, Y.-L., Dyso...

OCA — Wed, 26 Sep 2012 20:14:13 GMT

New page: '''Unreleased structure''' The entry 4h6j is ON HOLD Authors: Cardoso, R., Love, R.A., Nilsson, C., Bergqvist, S., Nowlin, D., Yan, Jiangli, Liu, K., Zhu, J, Chen, P., Deng, Y.-L., Dyso...

New page

'''Unreleased structure'''

The entry 4h6j is ON HOLD

Authors: Cardoso, R., Love, R.A., Nilsson, C., Bergqvist, S., Nowlin, D., Yan, Jiangli, Liu, K., Zhu, J, Chen, P., Deng, Y.-L., Dyson, H.J., Greig, M.J., Brooun, A.

Description: Identification of Cys 255 in HIF-1 as a novel site for development of covalent inhibitors of HIF-1 /ARNT PasB domain protein-protein interaction.