5adk - Revision history

OCA at 04:52, 25 May 2023

OCA — Thu, 25 May 2023 04:52:33 GMT

←Older revision		Revision as of 04:52, 25 May 2023
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	<StructureSection load='5adk' size='340' side='right'caption='[[5adk]], [[Resolution\|resolution]] 1.81Å' scene=''>		<StructureSection load='5adk' size='340' side='right'caption='[[5adk]], [[Resolution\|resolution]] 1.81Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5adk]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ADK OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5ADK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5adk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ADK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ADK FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7M3:7-[[3-[(DIMETHYLAMINO)METHYL]PHENOXY]METHYL]QUINOLIN-2-AMINE'>7M3</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</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" id="ligandDat"><scene name='pdbligand=7M3:7-[[3-[(DIMETHYLAMINO)METHYL]PHENOXY]METHYL]QUINOLIN-2-AMINE'>7M3</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5adk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5adk OCA], [https://pdbe.org/5adk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5adk RCSB], [https://www.ebi.ac.uk/pdbsum/5adk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5adk ProSAT]</span></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5ad4\|5ad4]], [[5ad5\|5ad5]], [[5ad6\|5ad6]], [[5ad7\|5ad7]], [[5ad8\|5ad8]], [[5ad9\|5ad9]], [[5ada\|5ada]], [[5adb\|5adb]], [[5adc\|5adc]], [[5add\|5add]], [[5ade\|5ade]], [[5adf\|5adf]], [[5adg\|5adg]], [[5adi\|5adi]], [[5adj\|5adj]], [[5adl\|5adl]], [[5adm\|5adm]], [[5adn\|5adn]]</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=5adk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5adk OCA], [~~http~~://pdbe.org/5adk PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5adk RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5adk PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5adk ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== 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.	+	[https://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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	==See Also==		==See Also==
-	*[[Nitric Oxide Synthase\|Nitric Oxide Synthase]]	+	*[[Nitric Oxide Synthase 3D structures\|Nitric Oxide Synthase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Bos taurus]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Li, H]]	+	[[Category: Li H]]
-	[[Category: Poulos~~, T L]]~~	+	[[Category: Poulos TL]]
-	~~[[Category: Inhibitor complex]]~~	+
-	~~[[Category: Nitric oxide synthase]]~~	+
-	~~[[Category: Oxidoreductase~~]]	+

OCA at 07:15, 3 July 2019

OCA — Wed, 03 Jul 2019 07:15:22 GMT

←Older revision		Revision as of 07:15, 3 July 2019
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	==Structure of bovine endothelial nitric oxide synthase heme domain in complex with 7-((3-(Dimethylamino)methyl)phenoxy)methyl)quinolin-2- amine==		==Structure of bovine endothelial nitric oxide synthase heme domain in complex with 7-((3-(Dimethylamino)methyl)phenoxy)methyl)quinolin-2- amine==
-	<StructureSection load='5adk' size='340' side='right' caption='[[5adk]], [[Resolution\|resolution]] 1.81Å' scene=''>	+	<StructureSection load='5adk' size='340' side='right'caption='[[5adk]], [[Resolution\|resolution]] 1.81Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5adk]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ADK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ADK FirstGlance]. <br>		<table><tr><td colspan='2'>[[5adk]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ADK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ADK FirstGlance]. <br>
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	</div>		</div>
	<div class="pdbe-citations 5adk" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5adk" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Nitric Oxide Synthase\|Nitric Oxide Synthase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Li, H]]		[[Category: Li, H]]
	[[Category: Poulos, T L]]		[[Category: Poulos, T L]]

OCA at 17:04, 18 August 2017

OCA — Fri, 18 Aug 2017 17:04:40 GMT

←Older revision		Revision as of 17:04, 18 August 2017
Line 1:		Line 1:
		+
	==Structure of bovine endothelial nitric oxide synthase heme domain in complex with 7-((3-(Dimethylamino)methyl)phenoxy)methyl)quinolin-2- amine==		==Structure of bovine endothelial nitric oxide synthase heme domain in complex with 7-((3-(Dimethylamino)methyl)phenoxy)methyl)quinolin-2- amine==
	<StructureSection load='5adk' size='340' side='right' caption='[[5adk]], [[Resolution\|resolution]] 1.81Å' scene=''>		<StructureSection load='5adk' size='340' side='right' caption='[[5adk]], [[Resolution\|resolution]] 1.81Å' scene=''>
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	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5ad4\|5ad4]], [[5ad5\|5ad5]], [[5ad6\|5ad6]], [[5ad7\|5ad7]], [[5ad8\|5ad8]], [[5ad9\|5ad9]], [[5ada\|5ada]], [[5adb\|5adb]], [[5adc\|5adc]], [[5add\|5add]], [[5ade\|5ade]], [[5adf\|5adf]], [[5adg\|5adg]], [[5adi\|5adi]], [[5adj\|5adj]], [[5adl\|5adl]], [[5adm\|5adm]], [[5adn\|5adn]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5ad4\|5ad4]], [[5ad5\|5ad5]], [[5ad6\|5ad6]], [[5ad7\|5ad7]], [[5ad8\|5ad8]], [[5ad9\|5ad9]], [[5ada\|5ada]], [[5adb\|5adb]], [[5adc\|5adc]], [[5add\|5add]], [[5ade\|5ade]], [[5adf\|5adf]], [[5adg\|5adg]], [[5adi\|5adi]], [[5adj\|5adj]], [[5adl\|5adl]], [[5adm\|5adm]], [[5adn\|5adn]]</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=5adk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5adk OCA], [http://pdbe.org/5adk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5adk RCSB], [http://www.ebi.ac.uk/pdbsum/5adk 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=5adk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5adk OCA], [http://pdbe.org/5adk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5adk RCSB], [http://www.ebi.ac.uk/pdbsum/5adk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5adk ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==

OCA at 18:57, 30 November 2015

OCA — Mon, 30 Nov 2015 18:57:53 GMT

←Older revision		Revision as of 18:57, 30 November 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Structure of bovine endothelial nitric oxide synthase heme domain in complex with 7-((3-(Dimethylamino)methyl)phenoxy)methyl)quinolin-2- amine==
		+	<StructureSection load='5adk' size='340' side='right' caption='[[5adk]], [[Resolution\|resolution]] 1.81Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5adk]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ADK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ADK FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7M3:7-[[3-[(DIMETHYLAMINO)METHYL]PHENOXY]METHYL]QUINOLIN-2-AMINE'>7M3</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</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">[[5ad4\|5ad4]], [[5ad5\|5ad5]], [[5ad6\|5ad6]], [[5ad7\|5ad7]], [[5ad8\|5ad8]], [[5ad9\|5ad9]], [[5ada\|5ada]], [[5adb\|5adb]], [[5adc\|5adc]], [[5add\|5add]], [[5ade\|5ade]], [[5adf\|5adf]], [[5adg\|5adg]], [[5adi\|5adi]], [[5adj\|5adj]], [[5adl\|5adl]], [[5adm\|5adm]], [[5adn\|5adn]]</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=5adk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5adk OCA], [http://pdbe.org/5adk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5adk RCSB], [http://www.ebi.ac.uk/pdbsum/5adk PDBsum]</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 ==
		+	Excess nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) is implicated in neurodegenerative disorders. As a result, inhibition of nNOS and reduction of NO levels is desirable therapeutically, but many nNOS inhibitors are poorly bioavailable. Promising members of our previously reported 2-aminoquinoline class of nNOS inhibitors, although orally bioavailable and brain-penetrant, suffer from unfavorable off-target binding to other CNS receptors, and they resemble known promiscuous binders. Rearranged phenyl ether- and aniline-linked 2-aminoquinoline derivatives were therefore designed to (a) disrupt the promiscuous binding pharmacophore and diminish off-target interactions and (b) preserve potency, isoform selectivity, and cell permeability. A series of these compounds was synthesized and tested against purified nNOS, endothelial NOS (eNOS), and inducible NOS (iNOS) enzymes. One compound, 20, displayed high potency, selectivity, and good human nNOS inhibition, and retained some permeability in a Caco-2 assay. Most promisingly, CNS receptor counterscreening revealed that this rearranged scaffold significantly reduces off-target binding.

-	~~The entry 5adk is ON HOLD until Paper Publication~~	+	Phenyl Ether- and Aniline-Containing 2-Aminoquinolines as Potent and Selective Inhibitors of Neuronal Nitric Oxide Synthase.,Cinelli MA, Li H, Pensa AV, Kang S, Roman LJ, Martasek P, Poulos TL, Silverman RB J Med Chem. 2015 Nov 12;58(21):8694-712. doi: 10.1021/acs.jmedchem.5b01330. Epub , 2015 Oct 27. PMID:26469213<ref>PMID:26469213</ref>

-	~~Authors: Li~~, H.~~, Poulos, T~~.L.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description: Structure of bovine endothelial nitric oxide synthase heme domain in complex with 7~~-~~((3~~-~~(Dimethylamino)methyl)phenoxy)methyl)quinolin-2-amine~~	+	<div class="pdbe-citations 5adk" style="background-color:#fffaf0;"></div>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	== References ==
-	~~[[Category: Poulos, T.L]]~~	+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Li, H]]		[[Category: Li, H]]
		+	[[Category: Poulos, T L]]
		+	[[Category: Inhibitor complex]]
		+	[[Category: Nitric oxide synthase]]
		+	[[Category: Oxidoreductase]]

OCA at 09:47, 2 September 2015

OCA — Wed, 02 Sep 2015 09:47:33 GMT

←Older revision		Revision as of 09:47, 2 September 2015
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5adk is ON HOLD	+	The entry 5adk is ON HOLD until Paper Publication

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

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

OCA — Wed, 26 Aug 2015 11:00:08 GMT

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

←Older revision

Revision as of 11:00, 26 August 2015

OCA: New page: '''Unreleased structure''' The entry 5adk is ON HOLD Authors: Li, H., Poulos, T.L. Description: Structure of bovine endothelial nitric oxide synthase heme domain in complex with 7-((3-...

OCA — Wed, 26 Aug 2015 11:00:05 GMT

New page: '''Unreleased structure''' The entry 5adk is ON HOLD Authors: Li, H., Poulos, T.L. Description: Structure of bovine endothelial nitric oxide synthase heme domain in complex with 7-((3-...

New page

'''Unreleased structure'''

The entry 5adk is ON HOLD

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

Description: Structure of bovine endothelial nitric oxide synthase heme domain in complex with 7-((3-(Dimethylamino)methyl)phenoxy)methyl)quinolin-2-amine
[[Category: Unreleased Structures]]
[[Category: Poulos, T.L]]
[[Category: Li, H]]