5uod - Revision history

OCA at 09:20, 1 January 2020

OCA — Wed, 01 Jan 2020 09:20:19 GMT

←Older revision		Revision as of 09:20, 1 January 2020
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	==Structure of bovine endothelial nitric oxide synthase heme domain in complex with 3-[(2-Amino-4-methylquinolin-7-yl)methoxy]-5-((methylamino)methyl)benzonitrile==		==Structure of bovine endothelial nitric oxide synthase heme domain in complex with 3-[(2-Amino-4-methylquinolin-7-yl)methoxy]-5-((methylamino)methyl)benzonitrile==
-	<StructureSection load='5uod' size='340' side='right' caption='[[5uod]], [[Resolution\|resolution]] 2.01Å' scene=''>	+	<StructureSection load='5uod' size='340' side='right'caption='[[5uod]], [[Resolution\|resolution]] 2.01Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5uod]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UOD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UOD FirstGlance]. <br>		<table><tr><td colspan='2'>[[5uod]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UOD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UOD FirstGlance]. <br>
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	</div>		</div>
	<div class="pdbe-citations 5uod" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5uod" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Nitric Oxide Synthase 3D structures\|Nitric Oxide Synthase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Bovin]]		[[Category: Bovin]]
		+	[[Category: Large Structures]]
	[[Category: Li, H]]		[[Category: Li, H]]
	[[Category: Poulos, T L]]		[[Category: Poulos, T L]]

OCA at 14:36, 6 November 2017

OCA — Mon, 06 Nov 2017 14:36:07 GMT

←Older revision		Revision as of 14:36, 6 November 2017
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	<StructureSection load='5uod' size='340' side='right' caption='[[5uod]], [[Resolution\|resolution]] 2.01Å' scene=''>		<StructureSection load='5uod' size='340' side='right' caption='[[5uod]], [[Resolution\|resolution]] 2.01Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5uod]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UOD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UOD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5uod]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UOD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UOD FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8EY:3-[(2-AMINO-4-METHYLQUINOLIN-7-YL)METHOXY]-5-[(METHYLAMINO)METHYL]BENZONITRILE'>8EY</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8EY:3-[(2-AMINO-4-METHYLQUINOLIN-7-YL)METHOXY]-5-[(METHYLAMINO)METHYL]BENZONITRILE'>8EY</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5unr\|5unr]], [[5unu\|5unu]], [[5unx\|5unx]], [[5unw\|5unw]], [[5uo1\|5uo1]], [[5uny\|5uny]], [[5uo3\|5uo3]], [[5uo5\|5uo5]], [[5uo4\|5uo4]], [[5uo6\|5uo6]], [[5uo7\|5uo7]], [[5uo8\|5uo8]], [[5uo2\|5uo2]], [[5uns\|5uns]], [[5unz\|5unz]], [[5uo0\|5uo0]], [[5unt\|5unt]], [[5unv\|5unv]], [[5uo9\|5uo9]], [[5uoa\|5uoa]], [[5uob\|5uob]], [[5uoc\|5uoc]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5unr\|5unr]], [[5unu\|5unu]], [[5unx\|5unx]], [[5unw\|5unw]], [[5uo1\|5uo1]], [[5uny\|5uny]], [[5uo3\|5uo3]], [[5uo5\|5uo5]], [[5uo4\|5uo4]], [[5uo6\|5uo6]], [[5uo7\|5uo7]], [[5uo8\|5uo8]], [[5uo2\|5uo2]], [[5uns\|5uns]], [[5unz\|5unz]], [[5uo0\|5uo0]], [[5unt\|5unt]], [[5unv\|5unv]], [[5uo9\|5uo9]], [[5uoa\|5uoa]], [[5uob\|5uob]], [[5uoc\|5uoc]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NOS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Nitric-oxide_synthase_(NADPH_dependent) Nitric-oxide synthase (NADPH dependent)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.39 1.14.13.39] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Nitric-oxide_synthase_(NADPH_dependent) Nitric-oxide synthase (NADPH dependent)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.39 1.14.13.39] </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=5uod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uod OCA], [http://pdbe.org/5uod PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uod RCSB], [http://www.ebi.ac.uk/pdbsum/5uod PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uod ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5uod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uod OCA], [http://pdbe.org/5uod PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uod RCSB], [http://www.ebi.ac.uk/pdbsum/5uod PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uod ProSAT]</span></td></tr>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Bovin]]
	[[Category: Li, H]]		[[Category: Li, H]]
	[[Category: Poulos, T L]]		[[Category: Poulos, T L]]

OCA at 12:58, 4 May 2017

OCA — Thu, 04 May 2017 12:58:44 GMT

←Older revision		Revision as of 12:58, 4 May 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5uod is ~~ON HOLD until Paper~~ Publication	+	==Structure of bovine endothelial nitric oxide synthase heme domain in complex with 3-[(2-Amino-4-methylquinolin-7-yl)methoxy]-5-((methylamino)methyl)benzonitrile==
		+	<StructureSection load='5uod' size='340' side='right' caption='[[5uod]], [[Resolution\|resolution]] 2.01Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5uod]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UOD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UOD FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8EY:3-[(2-AMINO-4-METHYLQUINOLIN-7-YL)METHOXY]-5-[(METHYLAMINO)METHYL]BENZONITRILE'>8EY</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5unr\|5unr]], [[5unu\|5unu]], [[5unx\|5unx]], [[5unw\|5unw]], [[5uo1\|5uo1]], [[5uny\|5uny]], [[5uo3\|5uo3]], [[5uo5\|5uo5]], [[5uo4\|5uo4]], [[5uo6\|5uo6]], [[5uo7\|5uo7]], [[5uo8\|5uo8]], [[5uo2\|5uo2]], [[5uns\|5uns]], [[5unz\|5unz]], [[5uo0\|5uo0]], [[5unt\|5unt]], [[5unv\|5unv]], [[5uo9\|5uo9]], [[5uoa\|5uoa]], [[5uob\|5uob]], [[5uoc\|5uoc]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Nitric-oxide_synthase_(NADPH_dependent) Nitric-oxide synthase (NADPH dependent)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.39 1.14.13.39] </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=5uod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uod OCA], [http://pdbe.org/5uod PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uod RCSB], [http://www.ebi.ac.uk/pdbsum/5uod PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uod ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/NOS3_BOVIN NOS3_BOVIN]] Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Neuronal nitric oxide synthase (nNOS) inhibition is a promising strategy to treat neurodegenerative disorders, but the development of nNOS inhibitors is often hindered by poor pharmacokinetics. We previously developed a class of membrane-permeable 2-aminoquinoline inhibitors and later rearranged the scaffold to decrease off-target binding. However, the resulting compounds had decreased permeability, low human nNOS activity, and low selectivity versus human eNOS. In this study, 5-substituted phenyl ether-linked aminoquinolines and derivatives were synthesized and assayed against purified NOS isoforms. 5-Cyano compounds are especially potent and selective rat and human nNOS inhibitors. Activity and selectivity are mediated by the binding of the cyano group to a new auxiliary pocket in nNOS. Potency was enhanced by methylation of the quinoline and by introduction of simple chiral moieties, resulting in a combination of hydrophobic and auxiliary pocket effects that yielded high ( approximately 500-fold) n/e selectivity. Importantly, the Caco-2 assay also revealed improved membrane permeability over previous compounds.

-	~~Authors~~: Li, H., Poulos, T.L.	+	Nitrile in the Hole: Discovery of a Small Auxiliary Pocket in Neuronal Nitric Oxide Synthase Leading to the Development of Potent and Selective 2-Aminoquinoline Inhibitors.,Cinelli MA, Li H, Chreifi G, Poulos TL, Silverman RB J Med Chem. 2017 Apr 19. doi: 10.1021/acs.jmedchem.7b00259. PMID:28422508<ref>PMID:28422508</ref>

-	~~Description: Structure~~ of ~~bovine endothelial nitric oxide synthase heme domain in complex with 3~~-~~[(2~~-~~Amino-4-methylquinolin-7-yl)methoxy]-5-((methylamino)methyl)benzonitrile~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
		+	<div class="pdbe-citations 5uod" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Li, H]]		[[Category: Li, H]]
-	[[Category: Poulos, T.L]]	+	[[Category: Poulos, T L]]
		+	[[Category: Heme enzyme]]
		+	[[Category: Inhibitor complex]]
		+	[[Category: Nitric oxide synthase]]
		+	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

OCA at 19:14, 15 March 2017

OCA — Wed, 15 Mar 2017 19:14:31 GMT

←Older revision		Revision as of 19:14, 15 March 2017
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	Description: Structure of bovine endothelial nitric oxide synthase heme domain in complex with 3-[(2-Amino-4-methylquinolin-7-yl)methoxy]-5-((methylamino)methyl)benzonitrile		Description: Structure of bovine endothelial nitric oxide synthase heme domain in complex with 3-[(2-Amino-4-methylquinolin-7-yl)methoxy]-5-((methylamino)methyl)benzonitrile
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Poulos, T.L]]
	[[Category: Li, H]]		[[Category: Li, H]]
		+	[[Category: Poulos, T.L]]

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

OCA — Thu, 09 Mar 2017 14:43:44 GMT

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

←Older revision

Revision as of 14:43, 9 March 2017

OCA: New page: '''Unreleased structure''' The entry 5uod is ON HOLD until Paper Publication Authors: Li, H., Poulos, T.L. Description: Structure of bovine endothelial nitric oxide synthase heme domai...

OCA — Thu, 09 Mar 2017 14:43:42 GMT

New page: '''Unreleased structure''' The entry 5uod is ON HOLD until Paper Publication Authors: Li, H., Poulos, T.L. Description: Structure of bovine endothelial nitric oxide synthase heme domai...

New page

'''Unreleased structure'''

The entry 5uod is ON HOLD until Paper Publication

Authors: Li, H., Poulos, T.L.

Description: Structure of bovine endothelial nitric oxide synthase heme domain in complex with 3-[(2-Amino-4-methylquinolin-7-yl)methoxy]-5-((methylamino)methyl)benzonitrile
[[Category: Unreleased Structures]]
[[Category: Poulos, T.L]]
[[Category: Li, H]]