5vv9 - Revision history

OCA at 13:59, 4 October 2023

OCA — Wed, 04 Oct 2023 13:59:21 GMT

←Older revision		Revision as of 13:59, 4 October 2023
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	<StructureSection load='5vv9' size='340' side='right'caption='[[5vv9]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='5vv9' size='340' side='right'caption='[[5vv9]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5vv9]] 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=5VV9 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5VV9 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5vv9]] 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=5VV9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VV9 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9OG:4-(2-{[(2-amino-4-methylquinolin-7-yl)methyl]amino}ethyl)benzonitrile'>9OG</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='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.5Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9OG:4-(2-{[(2-amino-4-methylquinolin-7-yl)methyl]amino}ethyl)benzonitrile'>9OG</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='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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5vv9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vv9 OCA], [https://pdbe.org/5vv9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vv9 RCSB], [https://www.ebi.ac.uk/pdbsum/5vv9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vv9 ProSAT]</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=5vv9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vv9 OCA], [~~http~~://pdbe.org/5vv9 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5vv9 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5vv9 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5vv9 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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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Bovin~~]]	+	[[Category: Bos taurus]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Li, H]]	+	[[Category: Li H]]
-	[[Category: Poulos~~, T L]]~~	+	[[Category: Poulos TL]]
-	~~[[Category: Heme enzyme]]~~	+
-	~~[[Category: Inhibitor complex]]~~	+
-	~~[[Category: Nitric oxide synthase]]~~	+
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex~~]]	+

OCA at 12:38, 25 December 2019

OCA — Wed, 25 Dec 2019 12:38:43 GMT

←Older revision		Revision as of 12:38, 25 December 2019
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	==Structure of bovine endothelial nitric oxide synthase heme domain in complex with 4-(2-(((2-Amino-4-methylquinolin-7-yl)methyl)amino)ethyl)benzonitrile==		==Structure of bovine endothelial nitric oxide synthase heme domain in complex with 4-(2-(((2-Amino-4-methylquinolin-7-yl)methyl)amino)ethyl)benzonitrile==
-	<StructureSection load='5vv9' size='340' side='right' caption='[[5vv9]], [[Resolution\|resolution]] 2.50Å' scene=''>	+	<StructureSection load='5vv9' size='340' side='right'caption='[[5vv9]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5vv9]] 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=5VV9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VV9 FirstGlance]. <br>		<table><tr><td colspan='2'>[[5vv9]] 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=5VV9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VV9 FirstGlance]. <br>
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	</div>		</div>
	<div class="pdbe-citations 5vv9" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5vv9" 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 00:14, 16 November 2017

OCA — Thu, 16 Nov 2017 00:14:05 GMT

←Older revision		Revision as of 00:14, 16 November 2017
Line 3:		Line 3:
	<StructureSection load='5vv9' size='340' side='right' caption='[[5vv9]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='5vv9' size='340' side='right' caption='[[5vv9]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5vv9]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VV9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VV9 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5vv9]] 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=5VV9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VV9 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9OG:4-(2-{[(2-amino-4-methylquinolin-7-yl)methyl]amino}ethyl)benzonitrile'>9OG</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=9OG:4-(2-{[(2-amino-4-methylquinolin-7-yl)methyl]amino}ethyl)benzonitrile'>9OG</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='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=5vv9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vv9 OCA], [http://pdbe.org/5vv9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vv9 RCSB], [http://www.ebi.ac.uk/pdbsum/5vv9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vv9 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=5vv9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vv9 OCA], [http://pdbe.org/5vv9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vv9 RCSB], [http://www.ebi.ac.uk/pdbsum/5vv9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vv9 ProSAT]</span></td></tr>
Line 24:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Bovin]]
	[[Category: Li, H]]		[[Category: Li, H]]
	[[Category: Poulos, T L]]		[[Category: Poulos, T L]]

OCA: Protected "5vv9" [edit=sysop:move=sysop]

OCA — Thu, 17 Aug 2017 06:00:44 GMT

Protected "5vv9" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:00, 17 August 2017

OCA: New page: ==Structure of bovine endothelial nitric oxide synthase heme domain in complex with 4-(2-(((2-Amino-4-methylquinolin-7-yl)methyl)amino)ethyl)benzonitrile==
OCA — Thu, 17 Aug 2017 06:00:42 GMT

New page: ==Structure of bovine endothelial nitric oxide synthase heme domain in complex with 4-(2-(((2-Amino-4-methylquinolin-7-yl)methyl)amino)ethyl)benzonitrile== <StructureSection load='5vv9' s...

New page

==Structure of bovine endothelial nitric oxide synthase heme domain in complex with 4-(2-(((2-Amino-4-methylquinolin-7-yl)methyl)amino)ethyl)benzonitrile==
<StructureSection load='5vv9' size='340' side='right' caption='[[5vv9]], [[Resolution|resolution]] 2.50Å' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5vv9]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VV9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VV9 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9OG:4-(2-{[(2-amino-4-methylquinolin-7-yl)methyl]amino}ethyl)benzonitrile'>9OG</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='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=5vv9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vv9 OCA], [http://pdbe.org/5vv9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vv9 RCSB], [http://www.ebi.ac.uk/pdbsum/5vv9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vv9 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) is a target for development of antineurodegenerative agents. Most nNOS inhibitors mimic l-arginine and have poor bioavailability. 2-Aminoquinolines showed promise as bioavailable nNOS inhibitors but suffered from low human nNOS inhibition, low selectivity versus human eNOS, and significant binding to other CNS targets. We aimed to improve human nNOS potency and selectivity and reduce off-target binding by (a) truncating the original scaffold or (b) introducing a hydrophilic group to interrupt the lipophilic, promiscuous pharmacophore and promote interaction with human nNOS-specific His342. We synthesized both truncated and polar 2-aminoquinoline derivatives and assayed them against recombinant NOS enzymes. Although aniline and pyridine derivatives interact with His342, benzonitriles conferred the best rat and human nNOS inhibition. Both introduction of a hydrophobic substituent next to the cyano group and aminoquinoline methylation considerably improved isoform selectivity. Most importantly, these modifications preserved Caco-2 permeability and reduced off-target CNS binding.

Hydrophilic, Potent, and Selective 7-Substituted 2-Aminoquinolines as Improved Human Neuronal Nitric Oxide Synthase Inhibitors.,Pensa AV, Cinelli MA, Li H, Chreifi G, Mukherjee P, Roman LJ, Martasek P, Poulos TL, Silverman RB J Med Chem. 2017 Aug 4. doi: 10.1021/acs.jmedchem.7b00835. PMID:28776992<ref>PMID:28776992</ref>

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5vv9" style="background-color:#fffaf0;"></div>
== References ==
<references/>
TOC
</StructureSection>
[[Category: Li, H]]
[[Category: Poulos, T L]]
[[Category: Heme enzyme]]
[[Category: Inhibitor complex]]
[[Category: Nitric oxide synthase]]
[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]