3tgm - Revision history

OCA at 13:27, 14 March 2024

OCA — Thu, 14 Mar 2024 13:27:58 GMT

←Older revision		Revision as of 13:27, 14 March 2024
Line 3:		Line 3:
	<StructureSection load='3tgm' size='340' side='right'caption='[[3tgm]], [[Resolution\|resolution]] 2.85Å' scene=''>		<StructureSection load='3tgm' size='340' side='right'caption='[[3tgm]], [[Resolution\|resolution]] 2.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3tgm]] 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=3TGM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TGM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3tgm]] 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=3TGM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TGM FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3TG:1-(1H-IMIDAZOL-1-YL)-4,4-DIPHENYLBUTAN-2-ONE'>3TG</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=HEZ:HEXANE-1,6-DIOL'>HEZ</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]] 2.85Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3czy\|3czy]], [[3hok\|3hok]], [[3k4f\|3k4f]], [[1n45\|1n45]]</div></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3TG:1-(1H-IMIDAZOL-1-YL)-4,4-DIPHENYLBUTAN-2-ONE'>3TG</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=HEZ:HEXANE-1,6-DIOL'>HEZ</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HMOX1, HO, HO1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Heme_oxygenase Heme oxygenase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.3 1.14.99.3] </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=3tgm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tgm OCA], [https://pdbe.org/3tgm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tgm RCSB], [https://www.ebi.ac.uk/pdbsum/3tgm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tgm 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=3tgm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tgm OCA], [https://pdbe.org/3tgm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tgm RCSB], [https://www.ebi.ac.uk/pdbsum/3tgm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tgm ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/HMOX1_HUMAN HMOX1_HUMAN]] Defects in HMOX1 are the cause of heme oxygenase 1 deficiency (HMOX1D) [MIM:[https://omim.org/entry/614034 614034]]. A disease characterized by impaired stress hematopoiesis, resulting in marked erythrocyte fragmentation and intravascular hemolysis, coagulation abnormalities, endothelial damage, and iron deposition in renal and hepatic tissues. Clinical features include persistent hemolytic anemia, asplenia, nephritis, generalized erythematous rash, growth retardation and hepatomegaly.<ref>PMID:9884342</ref>	+	[https://www.uniprot.org/uniprot/HMOX1_HUMAN HMOX1_HUMAN] Defects in HMOX1 are the cause of heme oxygenase 1 deficiency (HMOX1D) [MIM:[https://omim.org/entry/614034 614034]. A disease characterized by impaired stress hematopoiesis, resulting in marked erythrocyte fragmentation and intravascular hemolysis, coagulation abnormalities, endothelial damage, and iron deposition in renal and hepatic tissues. Clinical features include persistent hemolytic anemia, asplenia, nephritis, generalized erythematous rash, growth retardation and hepatomegaly.<ref>PMID:9884342</ref>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/HMOX1_HUMAN HMOX1_HUMAN]] Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the activity of heme oxygenase is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed.	+	[https://www.uniprot.org/uniprot/HMOX1_HUMAN HMOX1_HUMAN] Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the activity of heme oxygenase is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed.
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	The development of heme oxygenase (HO) inhibitors is critical in dissecting and understanding the HO system and for potential therapeutic applications. We have established a program to design and optimize HO inhibitors using structure-activity relationships in conjunction with X-ray crystallographic analyses. One of our previous complex crystal structures revealed a putative secondary hydrophobic binding pocket which could be exploited for a new design strategy by introducing a functional group that would fit into this potential site. To test this hypothesis and gain further insights into the structural basis of inhibitor binding, we have synthesized and characterized 1-(1H-imidazol-1-yl)-4,4-diphenyl-2-butanone (QC-308). Using a carbon monoxide (CO) formation assay on rat spleen microsomes, the compound was found to be approximately 15 times more potent (IC(50) = 0.27+/-0.07 microM) than its monophenyl analogue, which is already a potent compound in its own right (QC-65; IC(50) = 4.0+/-1.8 microM). The crystal structure of hHO-1 with QC-308 revealed that the second phenyl group in the western region of the compound is indeed accommodated by a definitive secondary proximal hydrophobic pocket. Thus, the two phenyl moieties are each stabilized by distinct hydrophobic pockets. This "double-clamp" binding offers additional inhibitor stabilization and provides a new route for improvement of human heme oxygenase inhibitors.	+
-		+
-	A novel, "double-clamp" binding mode for human heme oxygenase-1 inhibition.,Rahman MN, Vlahakis JZ, Vukomanovic D, Lee W, Szarek WA, Nakatsu K, Jia Z PLoS One. 2012;7(1):e29514. Epub 2012 Jan 19. PMID:22276118<ref>PMID:22276118</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3tgm" style="background-color:#fffaf0;"></div>~~	+

	==See Also==		==See Also==
Line 30:		Line 19:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Heme oxygenase]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Jia, Z]]	+	[[Category: Jia Z]]
-	[[Category: Rahman~~, M N]]~~	+	[[Category: Rahman MN]]
-	~~[[Category: Alpha helix]]~~	+
-	~~[[Category: Heme]]~~	+
-	~~[[Category: Microsome]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex~~]]	+

OCA at 16:57, 6 July 2022

OCA — Wed, 06 Jul 2022 16:57:06 GMT

←Older revision		Revision as of 16:57, 6 July 2022
Line 1:		Line 1:

	==X-Ray Crystal Structure of Human Heme Oxygenase-1 in Complex with 1-(1H-imidazol-1-yl)-4,4-diphenyl-2 butanone==		==X-Ray Crystal Structure of Human Heme Oxygenase-1 in Complex with 1-(1H-imidazol-1-yl)-4,4-diphenyl-2 butanone==
-	<StructureSection load='3tgm' size='340' side='right' caption='[[3tgm]], [[Resolution\|resolution]] 2.85Å' scene=''>	+	<StructureSection load='3tgm' size='340' side='right'caption='[[3tgm]], [[Resolution\|resolution]] 2.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3tgm]] 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=3TGM OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3TGM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3tgm]] 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=3TGM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TGM FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3TG:1-(1H-IMIDAZOL-1-YL)-4,4-DIPHENYLBUTAN-2-ONE'>3TG</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=HEZ:HEXANE-1,6-DIOL'>HEZ</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3TG:1-(1H-IMIDAZOL-1-YL)-4,4-DIPHENYLBUTAN-2-ONE'>3TG</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=HEZ:HEXANE-1,6-DIOL'>HEZ</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3czy\|3czy]], [[3hok\|3hok]], [[3k4f\|3k4f]], [[1n45\|1n45]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3czy\|3czy]], [[3hok\|3hok]], [[3k4f\|3k4f]], [[1n45\|1n45]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HMOX1, HO, HO1 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HMOX1, HO, HO1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Heme_oxygenase Heme oxygenase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.3 1.14.99.3] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Heme_oxygenase Heme oxygenase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.3 1.14.99.3] </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=3tgm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tgm OCA], [~~http~~://pdbe.org/3tgm PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3tgm RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3tgm PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3tgm 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=3tgm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tgm OCA], [https://pdbe.org/3tgm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tgm RCSB], [https://www.ebi.ac.uk/pdbsum/3tgm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tgm ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/HMOX1_HUMAN HMOX1_HUMAN]] Defects in HMOX1 are the cause of heme oxygenase 1 deficiency (HMOX1D) [MIM:[~~http~~://omim.org/entry/614034 614034]]. A disease characterized by impaired stress hematopoiesis, resulting in marked erythrocyte fragmentation and intravascular hemolysis, coagulation abnormalities, endothelial damage, and iron deposition in renal and hepatic tissues. Clinical features include persistent hemolytic anemia, asplenia, nephritis, generalized erythematous rash, growth retardation and hepatomegaly.<ref>PMID:9884342</ref>	+	[[https://www.uniprot.org/uniprot/HMOX1_HUMAN HMOX1_HUMAN]] Defects in HMOX1 are the cause of heme oxygenase 1 deficiency (HMOX1D) [MIM:[https://omim.org/entry/614034 614034]]. A disease characterized by impaired stress hematopoiesis, resulting in marked erythrocyte fragmentation and intravascular hemolysis, coagulation abnormalities, endothelial damage, and iron deposition in renal and hepatic tissues. Clinical features include persistent hemolytic anemia, asplenia, nephritis, generalized erythematous rash, growth retardation and hepatomegaly.<ref>PMID:9884342</ref>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/HMOX1_HUMAN HMOX1_HUMAN]] Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the activity of heme oxygenase is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed.	+	[[https://www.uniprot.org/uniprot/HMOX1_HUMAN HMOX1_HUMAN]] Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the activity of heme oxygenase is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 25:

	==See Also==		==See Also==
-	*[[Heme oxygenase\|Heme oxygenase]]	+	*[[Heme oxygenase 3D structures\|Heme oxygenase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 32:		Line 32:
	[[Category: Heme oxygenase]]		[[Category: Heme oxygenase]]
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Jia, Z]]		[[Category: Jia, Z]]
	[[Category: Rahman, M N]]		[[Category: Rahman, M N]]

OCA at 14:40, 4 August 2016

OCA — Thu, 04 Aug 2016 14:40:30 GMT

←Older revision		Revision as of 14:40, 4 August 2016
Line 1:		Line 1:
		+
	==X-Ray Crystal Structure of Human Heme Oxygenase-1 in Complex with 1-(1H-imidazol-1-yl)-4,4-diphenyl-2 butanone==		==X-Ray Crystal Structure of Human Heme Oxygenase-1 in Complex with 1-(1H-imidazol-1-yl)-4,4-diphenyl-2 butanone==
	<StructureSection load='3tgm' size='340' side='right' caption='[[3tgm]], [[Resolution\|resolution]] 2.85Å' scene=''>		<StructureSection load='3tgm' size='340' side='right' caption='[[3tgm]], [[Resolution\|resolution]] 2.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3tgm]] 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=3TGM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TGM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3tgm]] 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=3TGM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TGM FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3TG:1-(1H-IMIDAZOL-1-YL)-4,4-DIPHENYLBUTAN-2-ONE'>3TG</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=HEZ:HEXANE-1,6-DIOL'>HEZ</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3TG:1-(1H-IMIDAZOL-1-YL)-4,4-DIPHENYLBUTAN-2-ONE'>3TG</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=HEZ:HEXANE-1,6-DIOL'>HEZ</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3czy\|3czy]], [[3hok\|3hok]], [[3k4f\|3k4f]], [[1n45\|1n45]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3czy\|3czy]], [[3hok\|3hok]], [[3k4f\|3k4f]], [[1n45\|1n45]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HMOX1, HO, HO1 ([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">HMOX1, HO, HO1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Heme_oxygenase Heme oxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.3 1.14.99.3] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Heme_oxygenase Heme oxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.3 1.14.99.3] </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=3tgm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tgm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tgm RCSB], [http://www.ebi.ac.uk/pdbsum/3tgm 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=3tgm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tgm OCA], [http://pdbe.org/3tgm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3tgm RCSB], [http://www.ebi.ac.uk/pdbsum/3tgm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3tgm ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	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 3tgm" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 29:		Line 31:
	</StructureSection>		</StructureSection>
	[[Category: Heme oxygenase]]		[[Category: Heme oxygenase]]
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Jia, Z]]		[[Category: Jia, Z]]
	[[Category: Rahman, M N]]		[[Category: Rahman, M N]]

OCA at 06:42, 21 December 2014

OCA — Sun, 21 Dec 2014 06:42:29 GMT

←Older revision		Revision as of 06:42, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3tgm\| PDB=3tgm \| SCENE= }}~~	+	==X-Ray Crystal Structure of Human Heme Oxygenase-1 in Complex with 1-(1H-imidazol-1-yl)-4,4-diphenyl-2 butanone==
-	===X-Ray Crystal Structure of Human Heme Oxygenase-1 in Complex with 1-(1H-imidazol-1-yl)-4,4-diphenyl-2 butanone===	+	<StructureSection load='3tgm' size='340' side='right' caption='[[3tgm]], [[Resolution\|resolution]] 2.85Å' scene=''>
-	~~{{ABSTRACT_PUBMED_22276118}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3tgm]] 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=3TGM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TGM FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3TG:1-(1H-IMIDAZOL-1-YL)-4,4-DIPHENYLBUTAN-2-ONE'>3TG</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=HEZ:HEXANE-1,6-DIOL'>HEZ</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3czy\|3czy]], [[3hok\|3hok]], [[3k4f\|3k4f]], [[1n45\|1n45]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HMOX1, HO, HO1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Heme_oxygenase Heme oxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.3 1.14.99.3] </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=3tgm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tgm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tgm RCSB], [http://www.ebi.ac.uk/pdbsum/3tgm PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/HMOX1_HUMAN HMOX1_HUMAN]] Defects in HMOX1 are the cause of heme oxygenase 1 deficiency (HMOX1D) [MIM:[http://omim.org/entry/614034 614034]]. A disease characterized by impaired stress hematopoiesis, resulting in marked erythrocyte fragmentation and intravascular hemolysis, coagulation abnormalities, endothelial damage, and iron deposition in renal and hepatic tissues. Clinical features include persistent hemolytic anemia, asplenia, nephritis, generalized erythematous rash, growth retardation and hepatomegaly.<ref>PMID:9884342</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/HMOX1_HUMAN HMOX1_HUMAN]] Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the activity of heme oxygenase is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The development of heme oxygenase (HO) inhibitors is critical in dissecting and understanding the HO system and for potential therapeutic applications. We have established a program to design and optimize HO inhibitors using structure-activity relationships in conjunction with X-ray crystallographic analyses. One of our previous complex crystal structures revealed a putative secondary hydrophobic binding pocket which could be exploited for a new design strategy by introducing a functional group that would fit into this potential site. To test this hypothesis and gain further insights into the structural basis of inhibitor binding, we have synthesized and characterized 1-(1H-imidazol-1-yl)-4,4-diphenyl-2-butanone (QC-308). Using a carbon monoxide (CO) formation assay on rat spleen microsomes, the compound was found to be approximately 15 times more potent (IC(50) = 0.27+/-0.07 microM) than its monophenyl analogue, which is already a potent compound in its own right (QC-65; IC(50) = 4.0+/-1.8 microM). The crystal structure of hHO-1 with QC-308 revealed that the second phenyl group in the western region of the compound is indeed accommodated by a definitive secondary proximal hydrophobic pocket. Thus, the two phenyl moieties are each stabilized by distinct hydrophobic pockets. This "double-clamp" binding offers additional inhibitor stabilization and provides a new route for improvement of human heme oxygenase inhibitors.

-	~~==Disease==~~	+	A novel, "double-clamp" binding mode for human heme oxygenase-1 inhibition.,Rahman MN, Vlahakis JZ, Vukomanovic D, Lee W, Szarek WA, Nakatsu K, Jia Z PLoS One. 2012;7(1):e29514. Epub 2012 Jan 19. PMID:22276118<ref>PMID:22276118</ref>
-	~~[[http://www.uniprot.org/uniprot/HMOX1_HUMAN HMOX1_HUMAN]] Defects in HMOX1 are the cause of~~ heme oxygenase 1 ~~deficiency (HMOX1D) [MIM:[http://omim~~.~~org/entry/614034 614034]]. A disease characterized by impaired stress hematopoiesis~~, ~~resulting in marked erythrocyte fragmentation and intravascular hemolysis~~, ~~coagulation abnormalities~~, ~~endothelial damage~~, ~~and iron deposition in renal and hepatic tissues. Clinical features include persistent hemolytic anemia~~, ~~asplenia~~, ~~nephritis~~, ~~generalized erythematous rash, growth retardation and hepatomegaly~~.<ref>PMID:~~9884342~~</ref>	+

-	~~==Function==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[http:~~/~~/www.uniprot.org/uniprot/HMOX1_HUMAN HMOX1_HUMAN]] Heme oxygenase cleaves~~ the ~~heme ring at the alpha methene bridge to form biliverdin~~. ~~Biliverdin is subsequently converted to bilirubin by biliverdin reductase~~. ~~Under physiological conditions, the activity~~ of ~~heme oxygenase is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed~~.	+	</div>
-		+
-	~~==About this Structure==~~	+
-	~~[[3tgm]] 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=3TGM OCA].~~	+

	==See Also==		==See Also==
	*[[Heme oxygenase\|Heme oxygenase]]		*[[Heme oxygenase\|Heme oxygenase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:022276118</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Heme oxygenase]]		[[Category: Heme oxygenase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Jia, Z.]]	+	[[Category: Jia, Z]]
-	[[Category: Rahman, M N.]]	+	[[Category: Rahman, M N]]
	[[Category: Alpha helix]]		[[Category: Alpha helix]]
	[[Category: Heme]]		[[Category: Heme]]

OCA at 20:36, 24 March 2013

OCA — Sun, 24 Mar 2013 20:36:55 GMT

←Older revision		Revision as of 20:36, 24 March 2013
Line 1:		Line 1:
-	[[Image:3tgm.png\|left\|200px]]
-
	{{STRUCTURE_3tgm\| PDB=3tgm \| SCENE= }}		{{STRUCTURE_3tgm\| PDB=3tgm \| SCENE= }}
-
	===X-Ray Crystal Structure of Human Heme Oxygenase-1 in Complex with 1-(1H-imidazol-1-yl)-4,4-diphenyl-2 butanone===		===X-Ray Crystal Structure of Human Heme Oxygenase-1 in Complex with 1-(1H-imidazol-1-yl)-4,4-diphenyl-2 butanone===
		+	{{ABSTRACT_PUBMED_22276118}}

-	~~{{ABSTRACT_PUBMED_22276118}}~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/HMOX1_HUMAN HMOX1_HUMAN]] Defects in HMOX1 are the cause of heme oxygenase 1 deficiency (HMOX1D) [MIM:[http://omim.org/entry/614034 614034]]. A disease characterized by impaired stress hematopoiesis, resulting in marked erythrocyte fragmentation and intravascular hemolysis, coagulation abnormalities, endothelial damage, and iron deposition in renal and hepatic tissues. Clinical features include persistent hemolytic anemia, asplenia, nephritis, generalized erythematous rash, growth retardation and hepatomegaly.<ref>PMID:9884342</ref>
		+
		+	==Function==
		+	[[http://www.uniprot.org/uniprot/HMOX1_HUMAN HMOX1_HUMAN]] Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the activity of heme oxygenase is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed.

	==About this Structure==		==About this Structure==
Line 14:		Line 16:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:022276118</ref><references group="xtra"/>	+	<ref group="xtra">PMID:022276118</ref><references group="xtra"/><references/>
	[[Category: Heme oxygenase]]		[[Category: Heme oxygenase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]

OCA at 06:54, 20 October 2012

OCA — Sat, 20 Oct 2012 06:54:48 GMT

←Older revision		Revision as of 06:54, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[3tgm]] is a 2 chain structure ~~of [[Heme oxygenase]]~~ 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=3TGM OCA].	+	[[3tgm]] 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=3TGM OCA].

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

OCA at 14:42, 25 July 2012

OCA — Wed, 25 Jul 2012 14:42:42 GMT

←Older revision		Revision as of 14:42, 25 July 2012
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	[[Image:3tgm.png\|left\|200px]]		[[Image:3tgm.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3tgm", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3tgm\| PDB=3tgm \| SCENE= }}		{{STRUCTURE_3tgm\| PDB=3tgm \| SCENE= }}

	===X-Ray Crystal Structure of Human Heme Oxygenase-1 in Complex with 1-(1H-imidazol-1-yl)-4,4-diphenyl-2 butanone===		===X-Ray Crystal Structure of Human Heme Oxygenase-1 in Complex with 1-(1H-imidazol-1-yl)-4,4-diphenyl-2 butanone===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_22276118}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 22276118 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_22276118}}		{{ABSTRACT_PUBMED_22276118}}

	==About this Structure==		==About this Structure==
-	[[3tgm]] 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=3TGM OCA].	+	[[3tgm]] is a 2 chain structure of [[Heme oxygenase]] 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=3TGM OCA].
		+
		+	==See Also==
		+	*[[Heme oxygenase\|Heme oxygenase]]

	==Reference==		==Reference==

OCA at 05:56, 15 February 2012

OCA — Wed, 15 Feb 2012 05:56:51 GMT

←Older revision		Revision as of 05:56, 15 February 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3tgm.png\|left\|200px]]

-	The ~~entry 3tgm~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3tgm", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3tgm\| PDB=3tgm \| SCENE= }}

-	~~Authors: Rahman~~, ~~M.N., Jia, Z.~~	+	===X-Ray Crystal Structure of Human Heme Oxygenase-1 in Complex with 1-(1H-imidazol-1-yl)-4,4-diphenyl-2 butanone===

-	~~Description: X~~-~~Ray Crystal Structure of Human Heme Oxygenase-1 in Complex with 1~~-(~~1H-imidazol-1-yl~~)-4,4-~~diphenyl~~-2 ~~butanone~~	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_22276118}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 22276118 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_22276118}}
		+
		+	==About this Structure==
		+	[[3tgm]] 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=3TGM OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:022276118</ref><references group="xtra"/>
		+	[[Category: Heme oxygenase]]
		+	[[Category: Homo sapiens]]
		+	[[Category: Jia, Z.]]
		+	[[Category: Rahman, M N.]]
		+	[[Category: Alpha helix]]
		+	[[Category: Heme]]
		+	[[Category: Microsome]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

OCA at 06:37, 28 December 2011

OCA — Wed, 28 Dec 2011 06:37:32 GMT

←Older revision		Revision as of 06:37, 28 December 2011
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3tgm is ON HOLD	+	The entry 3tgm is ON HOLD until Paper Publication

	Authors: Rahman, M.N., Jia, Z.		Authors: Rahman, M.N., Jia, Z.

	Description: X-Ray Crystal Structure of Human Heme Oxygenase-1 in Complex with 1-(1H-imidazol-1-yl)-4,4-diphenyl-2 butanone		Description: X-Ray Crystal Structure of Human Heme Oxygenase-1 in Complex with 1-(1H-imidazol-1-yl)-4,4-diphenyl-2 butanone

OCA at 11:05, 14 December 2011

OCA — Wed, 14 Dec 2011 11:05:58 GMT

←Older revision		Revision as of 11:05, 14 December 2011
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3tgm is ON HOLD ~~until Paper Publication~~	+	The entry 3tgm is ON HOLD

	Authors: Rahman, M.N., Jia, Z.		Authors: Rahman, M.N., Jia, Z.

	Description: X-Ray Crystal Structure of Human Heme Oxygenase-1 in Complex with 1-(1H-imidazol-1-yl)-4,4-diphenyl-2 butanone		Description: X-Ray Crystal Structure of Human Heme Oxygenase-1 in Complex with 1-(1H-imidazol-1-yl)-4,4-diphenyl-2 butanone