6pow - Revision history

OCA at 07:33, 11 October 2023

OCA — Wed, 11 Oct 2023 07:33:07 GMT

←Older revision		Revision as of 07:33, 11 October 2023
Line 3:		Line 3:
	<StructureSection load='6pow' size='340' side='right'caption='[[6pow]], [[Resolution\|resolution]] 2.15Å' scene=''>		<StructureSection load='6pow' size='340' side='right'caption='[[6pow]], [[Resolution\|resolution]] 2.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6pow]] is a 4 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=6POW OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6POW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6pow]] is a 4 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=6POW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6POW FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GD:GADOLINIUM+ATOM'>GD</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=OUA:7-[5-(aminomethyl)pyridin-3-yl]-4-methylquinolin-2-amine'>OUA</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]] 2.15Å</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=9606 HUMAN])</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GD:GADOLINIUM+ATOM'>GD</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=OUA:7-[5-(aminomethyl)pyridin-3-yl]-4-methylquinolin-2-amine'>OUA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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'>[https://proteopedia.org/fgij/fg.htm?mol=6pow FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pow OCA], [https://pdbe.org/6pow PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pow RCSB], [https://www.ebi.ac.uk/pdbsum/6pow PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pow ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6pow FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pow OCA], [~~http~~://pdbe.org/6pow PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6pow RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6pow PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6pow ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/NOS3_HUMAN NOS3_HUMAN]] 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.<ref>PMID:17264164</ref> Isoform eNOS13C: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1.<ref>PMID:17264164</ref>	+	[https://www.uniprot.org/uniprot/NOS3_HUMAN NOS3_HUMAN] 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.<ref>PMID:17264164</ref> Isoform eNOS13C: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1.<ref>PMID:17264164</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 6pow" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6pow" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Nitric Oxide Synthase 3D structures\|Nitric Oxide Synthase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Chreifi, G]]	+	[[Category: Chreifi G]]
-	[[Category: Li, H]]	+	[[Category: Li H]]
-	[[Category: Poulos~~, T L]]~~	+	[[Category: Poulos TL]]
-	~~[[Category: Heme enzyme]]~~	+
-	~~[[Category: Nitric oxide synthase inhibitor]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Oxidoreductase-inhibitor complex~~]]	+

OCA at 07:23, 27 May 2020

OCA — Wed, 27 May 2020 07:23:24 GMT

←Older revision		Revision as of 07:23, 27 May 2020
Line 1:		Line 1:

	==Structure of human endotheial nitric oxide synthase heme domain in complex with 7-(5-(Aminomethyl)pyridin-3-yl)-4-methylquinolin-2-amine==		==Structure of human endotheial nitric oxide synthase heme domain in complex with 7-(5-(Aminomethyl)pyridin-3-yl)-4-methylquinolin-2-amine==
-	<StructureSection load='6pow' size='340' side='right'caption='[[6pow]]' scene=''>	+	<StructureSection load='6pow' size='340' side='right'caption='[[6pow]], [[Resolution\|resolution]] 2.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6POW OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6POW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6pow]] is a 4 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=6POW OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6POW FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6pow FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pow OCA], [http://pdbe.org/6pow PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pow RCSB], [http://www.ebi.ac.uk/pdbsum/6pow PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pow ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GD:GADOLINIUM+ATOM'>GD</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=OUA:7-[5-(aminomethyl)pyridin-3-yl]-4-methylquinolin-2-amine'>OUA</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=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/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://proteopedia.org/fgij/fg.htm?mol=6pow FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pow OCA], [http://pdbe.org/6pow PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pow RCSB], [http://www.ebi.ac.uk/pdbsum/6pow PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pow ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/NOS3_HUMAN NOS3_HUMAN]] 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.<ref>PMID:17264164</ref> Isoform eNOS13C: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1.<ref>PMID:17264164</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Inhibition of neuronal nitric oxide synthase (nNOS), an enzyme implicated in neurodegenerative disorders, is an attractive strategy for treating or preventing these diseases. We previously developed several classes of 2-aminoquinoline-based nNOS inhibitors, but these compounds had drawbacks including off-target promiscuity, low activity against human nNOS, and only modest selectivity for nNOS over related enzymes. In this study, we synthesized new nNOS inhibitors based on 7-phenyl-2-aminoquinoline and assayed them against rat and human nNOS, human eNOS, and murine and (in some cases) human iNOS. Compounds with a meta-relationship between the aminoquinoline and a positively charged tail moiety were potent and had up to nearly 900-fold selectivity for human nNOS over human eNOS. X-ray crystallography indicates that the amino groups of some compounds occupy a water-filled pocket surrounding an nNOS-specific aspartate residue (absent in eNOS). This interaction was confirmed by mutagenesis studies, making 7-phenyl-2-aminoquinolines the first aminoquinolines to interact with this residue.
		+
		+	First Contact: 7-Phenyl-2-Aminoquinolines, Potent and Selective Neuronal Nitric Oxide Synthase Inhibitors That Target an Isoform-Specific Aspartate.,Cinelli MA, Reidl CT, Li H, Chreifi G, Poulos TL, Silverman RB J Med Chem. 2020 Apr 17. doi: 10.1021/acs.jmedchem.9b01573. PMID:32302123<ref>PMID:32302123</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6pow" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Chreifi G]]	+	[[Category: Chreifi, G]]
-	[[Category: Li H]]	+	[[Category: Li, H]]
-	[[Category: Poulos TL]]	+	[[Category: Poulos, T L]]
		+	[[Category: Heme enzyme]]
		+	[[Category: Nitric oxide synthase inhibitor]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Oxidoreductase-inhibitor complex]]

OCA at 06:43, 29 April 2020

OCA — Wed, 29 Apr 2020 06:43:38 GMT

←Older revision		Revision as of 06:43, 29 April 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 6pow is ON HOLD until Paper Publication~~	+	==Structure of human endotheial nitric oxide synthase heme domain in complex with 7-(5-(Aminomethyl)pyridin-3-yl)-4-methylquinolin-2-amine==
-		+	<StructureSection load='6pow' size='340' side='right'caption='[[6pow]]' scene=''>
-	~~Authors: Chreifi, G., Li, H., Poulos, T.L.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6POW OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6POW FirstGlance]. <br>
-	~~Description:~~ Structure of human endotheial nitric oxide synthase heme domain in complex with 7-(5-(Aminomethyl)pyridin-3-yl)-4-methylquinolin-2-amine	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6pow FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pow OCA], [http://pdbe.org/6pow PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pow RCSB], [http://www.ebi.ac.uk/pdbsum/6pow PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pow ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: Li, H]]	+	__TOC__
-	[[Category: Chreifi, G]]	+	</StructureSection>
-	[[Category: Poulos~~, T.L~~]]	+	[[Category: Large Structures]]
		+	[[Category: Chreifi G]]
		+	[[Category: Li H]]
		+	[[Category: Poulos TL]]

OCA at 04:28, 24 July 2019

OCA — Wed, 24 Jul 2019 04:28:02 GMT

←Older revision		Revision as of 04:28, 24 July 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6pow is ON HOLD	+	The entry 6pow is ON HOLD until Paper Publication

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

OCA: Protected "6pow" [edit=sysop:move=sysop]

OCA — Wed, 17 Jul 2019 09:02:14 GMT

Protected "6pow" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:02, 17 July 2019

OCA: New page: '''Unreleased structure''' The entry 6pow is ON HOLD Authors: Chreifi, G., Li, H., Poulos, T.L. Description: Structure of human endotheial nitric oxide synthase heme domain in complex ...

OCA — Wed, 17 Jul 2019 09:02:12 GMT

New page: '''Unreleased structure''' The entry 6pow is ON HOLD Authors: Chreifi, G., Li, H., Poulos, T.L. Description: Structure of human endotheial nitric oxide synthase heme domain in complex ...

New page

'''Unreleased structure'''

The entry 6pow is ON HOLD

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

Description: Structure of human endotheial nitric oxide synthase heme domain in complex with 7-(5-(Aminomethyl)pyridin-3-yl)-4-methylquinolin-2-amine
[[Category: Unreleased Structures]]
[[Category: Li, H]]
[[Category: Chreifi, G]]
[[Category: Poulos, T.L]]