1h2k - Revision history

OCA at 08:52, 9 May 2024

OCA — Thu, 09 May 2024 08:52:37 GMT

←Older revision		Revision as of 08:52, 9 May 2024
Line 20:		Line 20:
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1h2k ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1h2k ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The activity of the transcription factor hypoxia-inducible factor (HIF) is regulated by oxygen-dependent hydroxylation. Under normoxic conditions, hydroxylation of proline residues triggers destruction of its alpha-subunit while hydroxylation of Asn(803) in the C-terminal transactivation domain of HIF-1 alpha (CAD) prevents its interaction with p300. Here we report crystal structures of the asparagine hydroxylase (factor-inhibiting HIF, FIH) complexed with Fe((II)), 2-oxoglutarate cosubstrate, and CAD fragments, which reveal the structural basis of HIF modification. CAD binding to FIH occurs via an induced fit process at two distinct interaction sites. At the hydroxylation site CAD adopts a loop conformation, contrasting with a helical conformation for the same residues when bound to p300. Asn(803) of CAD is buried and precisely orientated in the active site such that hydroxylation occurs at its beta-carbon. Together with structures with the inhibitors Zn((II)) and N-oxaloylglycine, analysis of the FIH-CAD complexes will assist design of hydroxylase inhibitors with proangiogenic properties. Conserved structural motifs within FIH imply it is one of an extended family of Fe((II)) oxygenases involved in gene regulation.
		+
		+	Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alpha.,Elkins JM, Hewitson KS, McNeill LA, Seibel JF, Schlemminger I, Pugh CW, Ratcliffe PJ, Schofield CJ J Biol Chem. 2003 Jan 17;278(3):1802-6. Epub 2002 Nov 21. PMID:12446723<ref>PMID:12446723</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 1h2k" style="background-color:#fffaf0;"></div>

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

OCA at 11:27, 27 March 2024

OCA — Wed, 27 Mar 2024 11:27:11 GMT

←Older revision		Revision as of 11:27, 27 March 2024
Line 3:		Line 3:
	<StructureSection load='1h2k' size='340' side='right'caption='[[1h2k]], [[Resolution\|resolution]] 2.15Å' scene=''>		<StructureSection load='1h2k' size='340' side='right'caption='[[1h2k]], [[Resolution\|resolution]] 2.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1h2k]] is a 2 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=1H2K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H2K FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1h2k]] 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=1H2K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H2K FirstGlance]. <br>
-	</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=OGA:N-OXALYLGLYCINE'>OGA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene~~></td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.15Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1d7g\|1d7g]], [[1h2l\|1h2l]], [[1h2m\|1h2m]], [[1h2n\|1h2n]], [[1l8c\|1l8c]], [[1lm8\|1lm8]], [[1lqb\|1lqb]]</div></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=OGA:N-OXALYLGLYCINE'>OGA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=1h2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h2k OCA], [https://pdbe.org/1h2k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h2k RCSB], [https://www.ebi.ac.uk/pdbsum/1h2k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h2k 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=1h2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h2k OCA], [https://pdbe.org/1h2k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h2k RCSB], [https://www.ebi.ac.uk/pdbsum/1h2k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h2k ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[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> [[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/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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 20:		Line 20:
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1h2k ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1h2k ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The activity of the transcription factor hypoxia-inducible factor (HIF) is regulated by oxygen-dependent hydroxylation. Under normoxic conditions, hydroxylation of proline residues triggers destruction of its alpha-subunit while hydroxylation of Asn(803) in the C-terminal transactivation domain of HIF-1 alpha (CAD) prevents its interaction with p300. Here we report crystal structures of the asparagine hydroxylase (factor-inhibiting HIF, FIH) complexed with Fe((II)), 2-oxoglutarate cosubstrate, and CAD fragments, which reveal the structural basis of HIF modification. CAD binding to FIH occurs via an induced fit process at two distinct interaction sites. At the hydroxylation site CAD adopts a loop conformation, contrasting with a helical conformation for the same residues when bound to p300. Asn(803) of CAD is buried and precisely orientated in the active site such that hydroxylation occurs at its beta-carbon. Together with structures with the inhibitors Zn((II)) and N-oxaloylglycine, analysis of the FIH-CAD complexes will assist design of hydroxylase inhibitors with proangiogenic properties. Conserved structural motifs within FIH imply it is one of an extended family of Fe((II)) oxygenases involved in gene regulation.
-
-	Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alpha.,Elkins JM, Hewitson KS, McNeill LA, Seibel JF, Schlemminger I, Pugh CW, Ratcliffe PJ, Schofield CJ J Biol Chem. 2003 Jan 17;278(3):1802-6. Epub 2002 Nov 21. PMID:12446723<ref>PMID:12446723</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 1h2k" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Factor inhibiting HIF\|Factor inhibiting HIF]]		*[[Factor inhibiting HIF\|Factor inhibiting HIF]]
	*[[Hypoxia-Inducible factor 1 alpha inhibitor\|Hypoxia-Inducible factor 1 alpha inhibitor]]		*[[Hypoxia-Inducible factor 1 alpha inhibitor\|Hypoxia-Inducible factor 1 alpha inhibitor]]
		+	*[[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: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Elkins~~, J M~~]]	+	[[Category: Elkins JM]]
-	[[Category: Hewitson~~, K S~~]]	+	[[Category: Hewitson KS]]
-	[[Category: McNeill~~, L A~~]]	+	[[Category: McNeill LA]]
-	[[Category: Schlemminger, I]]	+	[[Category: Schlemminger I]]
-	[[Category: Schofield~~, C J~~]]	+	[[Category: Schofield CJ]]
-	[[Category: Seibel~~, J F]]~~	+	[[Category: Seibel JF]]
-	~~[[Category: 2- oxoglutarate]]~~	+
-	~~[[Category: Asparaginyl hydroxylase]]~~	+
-	~~[[Category: Dsbh]]~~	+
-	~~[[Category: Fih]]~~	+
-	~~[[Category: Hif]]~~	+
-	~~[[Category: Hypoxia]]~~	+
-	~~[[Category: Oxygenase]]~~	+
-	~~[[Category: Phosphorylation]]~~	+
-	~~[[Category: Transcription]]~~	+
-	~~[[Category: Transcription activator-inhibitor complex~~]]	+

OCA at 09:17, 8 September 2021

OCA — Wed, 08 Sep 2021 09:17:11 GMT

←Older revision		Revision as of 09:17, 8 September 2021
Line 3:		Line 3:
	<StructureSection load='1h2k' size='340' side='right'caption='[[1h2k]], [[Resolution\|resolution]] 2.15Å' scene=''>		<StructureSection load='1h2k' size='340' side='right'caption='[[1h2k]], [[Resolution\|resolution]] 2.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1h2k]] 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=1H2K OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1H2K FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1h2k]] is a 2 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=1H2K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H2K 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=OGA:N-OXALYLGLYCINE'>OGA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1d7g\|1d7g]], [[1h2l\|1h2l]], [[1h2m\|1h2m]], [[1h2n\|1h2n]], [[1l8c\|1l8c]], [[1lm8\|1lm8]], [[1lqb\|1lqb]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1d7g\|1d7g]], [[1h2l\|1h2l]], [[1h2m\|1h2m]], [[1h2n\|1h2n]], [[1l8c\|1l8c]], [[1lm8\|1lm8]], [[1lqb\|1lqb]]</div></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=1h2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h2k OCA], [~~http~~://pdbe.org/1h2k PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1h2k RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1h2k PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1h2k 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=1h2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h2k OCA], [https://pdbe.org/1h2k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h2k RCSB], [https://www.ebi.ac.uk/pdbsum/1h2k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h2k 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/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/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/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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 32:		Line 32:
	==See Also==		==See Also==
	*[[Factor inhibiting HIF\|Factor inhibiting HIF]]		*[[Factor inhibiting HIF\|Factor inhibiting HIF]]
		+	*[[Hypoxia-Inducible factor 1 alpha inhibitor\|Hypoxia-Inducible factor 1 alpha inhibitor]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 09:40, 27 November 2019

OCA — Wed, 27 Nov 2019 09:40:45 GMT

←Older revision		Revision as of 09:40, 27 November 2019
Line 1:		Line 1:

	==Factor Inhibiting HIF-1 alpha in complex with HIF-1 alpha fragment peptide==		==Factor Inhibiting HIF-1 alpha in complex with HIF-1 alpha fragment peptide==
-	<StructureSection load='1h2k' size='340' side='right' caption='[[1h2k]], [[Resolution\|resolution]] 2.15Å' scene=''>	+	<StructureSection load='1h2k' size='340' side='right'caption='[[1h2k]], [[Resolution\|resolution]] 2.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1h2k]] 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=1H2K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1H2K FirstGlance]. <br>		<table><tr><td colspan='2'>[[1h2k]] 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=1H2K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1H2K FirstGlance]. <br>
Line 29:		Line 29:
	</div>		</div>
	<div class="pdbe-citations 1h2k" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1h2k" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Factor inhibiting HIF\|Factor inhibiting HIF]]
	== References ==		== References ==
	<references/>		<references/>
Line 34:		Line 37:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Elkins, J M]]		[[Category: Elkins, J M]]
	[[Category: Hewitson, K S]]		[[Category: Hewitson, K S]]

OCA at 06:13, 3 January 2018

OCA — Wed, 03 Jan 2018 06:13:56 GMT

←Older revision		Revision as of 06:13, 3 January 2018
Line 1:		Line 1:
-	==~~FACTOR INHIBITING~~ HIF-1 ~~ALPHA IN COMPLEX WITH~~ HIF-1 ~~ALPHA FRAGMENT PEPTIDE~~==	+
		+	==Factor Inhibiting HIF-1 alpha in complex with HIF-1 alpha fragment peptide==
	<StructureSection load='1h2k' size='340' side='right' caption='[[1h2k]], [[Resolution\|resolution]] 2.15Å' scene=''>		<StructureSection load='1h2k' size='340' side='right' caption='[[1h2k]], [[Resolution\|resolution]] 2.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
Line 5:		Line 6:
	</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=OGA:N-OXALYLGLYCINE'>OGA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1d7g\|1d7g]], [[1h2l\|1h2l]], [[1h2m\|1h2m]], [[1h2n\|1h2n]], [[1l8c\|1l8c]], [[1lm8\|1lm8]], [[1lqb\|1lqb]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1d7g\|1d7g]], [[1h2l\|1h2l]], [[1h2m\|1h2m]], [[1h2n\|1h2n]], [[1l8c\|1l8c]], [[1lm8\|1lm8]], [[1lqb\|1lqb]]</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=1h2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h2k OCA], [http://pdbe.org/1h2k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1h2k RCSB], [http://www.ebi.ac.uk/pdbsum/1h2k 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=1h2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h2k OCA], [http://pdbe.org/1h2k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1h2k RCSB], [http://www.ebi.ac.uk/pdbsum/1h2k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1h2k ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 13:		Line 14:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h2/1h2k_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h2/1h2k_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 28:		Line 29:
	</div>		</div>
	<div class="pdbe-citations 1h2k" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1h2k" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Factor inhibiting HIF\|Factor inhibiting HIF]]
	== References ==		== References ==
	<references/>		<references/>
Line 38:		Line 36:
	[[Category: Elkins, J M]]		[[Category: Elkins, J M]]
	[[Category: Hewitson, K S]]		[[Category: Hewitson, K S]]
-	[[Category: ~~Mcneill~~, L A]]	+	[[Category: McNeill, L A]]
	[[Category: Schlemminger, I]]		[[Category: Schlemminger, I]]
	[[Category: Schofield, C J]]		[[Category: Schofield, C J]]

OCA at 21:58, 7 February 2016

OCA — Sun, 07 Feb 2016 21:58:59 GMT

←Older revision		Revision as of 21:58, 7 February 2016
Line 17:		Line 17:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1h2k ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 05:19, 10 September 2015

OCA — Thu, 10 Sep 2015 05:19:06 GMT

←Older revision		Revision as of 05:19, 10 September 2015
Line 2:		Line 2:
	<StructureSection load='1h2k' size='340' side='right' caption='[[1h2k]], [[Resolution\|resolution]] 2.15Å' scene=''>		<StructureSection load='1h2k' size='340' side='right' caption='[[1h2k]], [[Resolution\|resolution]] 2.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1h2k]] 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=1H2K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1H2K FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1h2k]] 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=1H2K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1H2K 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=OGA:N-OXALYLGLYCINE'>OGA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1d7g\|1d7g]], [[1h2l\|1h2l]], [[1h2m\|1h2m]], [[1h2n\|1h2n]], [[1l8c\|1l8c]], [[1lm8\|1lm8]], [[1lqb\|1lqb]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1d7g\|1d7g]], [[1h2l\|1h2l]], [[1h2m\|1h2m]], [[1h2n\|1h2n]], [[1l8c\|1l8c]], [[1lm8\|1lm8]], [[1lqb\|1lqb]]</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=1h2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h2k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1h2k RCSB], [http://www.ebi.ac.uk/pdbsum/1h2k 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=1h2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h2k OCA], [http://pdbe.org/1h2k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1h2k RCSB], [http://www.ebi.ac.uk/pdbsum/1h2k PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 27:		Line 27:
	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 1h2k" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 34:		Line 35:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Elkins, J M]]		[[Category: Elkins, J M]]
	[[Category: Hewitson, K S]]		[[Category: Hewitson, K S]]

OCA at 18:30, 24 December 2014

OCA — Wed, 24 Dec 2014 18:30:17 GMT

←Older revision		Revision as of 18:30, 24 December 2014
Line 7:		Line 7:
	<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=1h2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h2k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1h2k RCSB], [http://www.ebi.ac.uk/pdbsum/1h2k 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=1h2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h2k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1h2k RCSB], [http://www.ebi.ac.uk/pdbsum/1h2k PDBsum]</span></td></tr>
	</table>		</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> [[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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]

OCA at 20:03, 22 December 2014

OCA — Mon, 22 Dec 2014 20:03:07 GMT

←Older revision		Revision as of 20:03, 22 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1h2k]] 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=1H2K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1H2K FirstGlance]. <br>		<table><tr><td colspan='2'>[[1h2k]] 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=1H2K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1H2K FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><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=OGA:N-OXALYLGLYCINE'>OGA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1d7g\|1d7g]], [[1h2l\|1h2l]], [[1h2m\|1h2m]], [[1h2n\|1h2n]], [[1l8c\|1l8c]], [[1lm8\|1lm8]], [[1lqb\|1lqb]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1d7g\|1d7g]], [[1h2l\|1h2l]], [[1h2m\|1h2m]], [[1h2n\|1h2n]], [[1l8c\|1l8c]], [[1lm8\|1lm8]], [[1lqb\|1lqb]]</td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1h2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h2k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1h2k RCSB], [http://www.ebi.ac.uk/pdbsum/1h2k 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=1h2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h2k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1h2k RCSB], [http://www.ebi.ac.uk/pdbsum/1h2k PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 33:		Line 33:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Elkins, J M.]]	+	[[Category: Elkins, J M]]
-	[[Category: Hewitson, K S.]]	+	[[Category: Hewitson, K S]]
-	[[Category: Mcneill, L A.]]	+	[[Category: Mcneill, L A]]
-	[[Category: Schlemminger, I.]]	+	[[Category: Schlemminger, I]]
-	[[Category: Schofield, C J.]]	+	[[Category: Schofield, C J]]
-	[[Category: Seibel, J F.]]	+	[[Category: Seibel, J F]]
	[[Category: 2- oxoglutarate]]		[[Category: 2- oxoglutarate]]
	[[Category: Asparaginyl hydroxylase]]		[[Category: Asparaginyl hydroxylase]]

OCA at 09:53, 28 September 2014

OCA — Sun, 28 Sep 2014 09:53:52 GMT

←Older revision		Revision as of 09:53, 28 September 2014
Line 1:		Line 1:
-	[[~~Image:~~1h2k.~~png~~\|~~left~~\|200px]]	+	==FACTOR INHIBITING HIF-1 ALPHA IN COMPLEX WITH HIF-1 ALPHA FRAGMENT PEPTIDE==
		+	<StructureSection load='1h2k' size='340' side='right' caption='[[1h2k]], [[Resolution\|resolution]] 2.15Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1h2k]] 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=1H2K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1H2K FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1d7g\|1d7g]], [[1h2l\|1h2l]], [[1h2m\|1h2m]], [[1h2n\|1h2n]], [[1l8c\|1l8c]], [[1lm8\|1lm8]], [[1lqb\|1lqb]]</td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1h2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h2k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1h2k RCSB], [http://www.ebi.ac.uk/pdbsum/1h2k PDBsum]</span></td></tr>
		+	<table>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h2/1h2k_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The activity of the transcription factor hypoxia-inducible factor (HIF) is regulated by oxygen-dependent hydroxylation. Under normoxic conditions, hydroxylation of proline residues triggers destruction of its alpha-subunit while hydroxylation of Asn(803) in the C-terminal transactivation domain of HIF-1 alpha (CAD) prevents its interaction with p300. Here we report crystal structures of the asparagine hydroxylase (factor-inhibiting HIF, FIH) complexed with Fe((II)), 2-oxoglutarate cosubstrate, and CAD fragments, which reveal the structural basis of HIF modification. CAD binding to FIH occurs via an induced fit process at two distinct interaction sites. At the hydroxylation site CAD adopts a loop conformation, contrasting with a helical conformation for the same residues when bound to p300. Asn(803) of CAD is buried and precisely orientated in the active site such that hydroxylation occurs at its beta-carbon. Together with structures with the inhibitors Zn((II)) and N-oxaloylglycine, analysis of the FIH-CAD complexes will assist design of hydroxylase inhibitors with proangiogenic properties. Conserved structural motifs within FIH imply it is one of an extended family of Fe((II)) oxygenases involved in gene regulation.

-	~~{{STRUCTURE_1h2k\| PDB=1h2k \| SCENE= }}~~	+	Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alpha.,Elkins JM, Hewitson KS, McNeill LA, Seibel JF, Schlemminger I, Pugh CW, Ratcliffe PJ, Schofield CJ J Biol Chem. 2003 Jan 17;278(3):1802-6. Epub 2002 Nov 21. PMID:12446723<ref>PMID:12446723</ref>

-	~~===FACTOR INHIBITING HIF-1 ALPHA IN COMPLEX WITH HIF-1 ALPHA FRAGMENT PEPTIDE===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_12446723}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[1h2k]] 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=1H2K OCA].~~	+

	==See Also==		==See Also==
	*[[Factor inhibiting HIF\|Factor inhibiting HIF]]		*[[Factor inhibiting HIF\|Factor inhibiting HIF]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:012446723<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Elkins, J M.]]		[[Category: Elkins, J M.]]