6nhf - Revision history

OCA at 06:53, 11 October 2023

2023-10-11T06:53:56Z

←Older revision		Revision as of 06:53, 11 October 2023
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	<StructureSection load='6nhf' size='340' side='right'caption='[[6nhf]], [[Resolution\|resolution]] 1.83Å' scene=''>		<StructureSection load='6nhf' size='340' side='right'caption='[[6nhf]], [[Resolution\|resolution]] 1.83Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6nhf]] 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=6NHF OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6NHF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6nhf]] 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=6NHF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NHF FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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=KNV:6-[2-(2,3-difluoro-5-{2-[(2S)-1-methylazetidin-2-yl]ethyl}phenyl)ethyl]-4-methylpyridin-2-amine'>KNV</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]] 1.83Å</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=6nhf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nhf OCA], [~~http~~://pdbe.org/6nhf PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6nhf RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6nhf PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6nhf ProSAT]</span></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=KNV:6-[2-(2,3-difluoro-5-{2-[(2S)-1-methylazetidin-2-yl]ethyl}phenyl)ethyl]-4-methylpyridin-2-amine'>KNV</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6nhf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nhf OCA], [https://pdbe.org/6nhf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nhf RCSB], [https://www.ebi.ac.uk/pdbsum/6nhf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nhf ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[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 ==
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	__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: Nitric oxide synthase inhibitor complex heme enzyme]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex~~]]	+

OCA at 10:34, 4 December 2019

2019-12-04T10:34:38Z

←Older revision		Revision as of 10:34, 4 December 2019
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	</div>		</div>
	<div class="pdbe-citations 6nhf" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6nhf" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Nitric Oxide Synthase 3D structures\|Nitric Oxide Synthase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:12, 27 March 2019

2019-03-27T07:12:57Z

←Older revision		Revision as of 07:12, 27 March 2019
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	<StructureSection load='6nhf' size='340' side='right'caption='[[6nhf]], [[Resolution\|resolution]] 1.83Å' scene=''>		<StructureSection load='6nhf' size='340' side='right'caption='[[6nhf]], [[Resolution\|resolution]] 1.83Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6nhf]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NHF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NHF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6nhf]] 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=6NHF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NHF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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=KNV:6-[2-(2,3-difluoro-5-{2-[(2S)-1-methylazetidin-2-yl]ethyl}phenyl)ethyl]-4-methylpyridin-2-amine'>KNV</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=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=KNV:6-[2-(2,3-difluoro-5-{2-[(2S)-1-methylazetidin-2-yl]ethyl}phenyl)ethyl]-4-methylpyridin-2-amine'>KNV</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=6nhf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nhf OCA], [http://pdbe.org/6nhf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nhf RCSB], [http://www.ebi.ac.uk/pdbsum/6nhf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nhf 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=6nhf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nhf OCA], [http://pdbe.org/6nhf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nhf RCSB], [http://www.ebi.ac.uk/pdbsum/6nhf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nhf ProSAT]</span></td></tr>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Chreifi, G]]		[[Category: Chreifi, G]]

OCA at 12:22, 13 March 2019

2019-03-13T12:22:23Z

←Older revision		Revision as of 12:22, 13 March 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6nhf is ~~ON HOLD until Paper~~ Publication	+	==Structure of human endothelial nitric oxide synthase heme domain in complex with (S)-6-(2,3-difluoro-5-(2-(1-methylazetidin-2-yl)ethyl)phenethyl)-4-methylpyridin-2-amine==
		+	<StructureSection load='6nhf' size='340' side='right'caption='[[6nhf]], [[Resolution\|resolution]] 1.83Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6nhf]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NHF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NHF FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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=KNV:6-[2-(2,3-difluoro-5-{2-[(2S)-1-methylazetidin-2-yl]ethyl}phenyl)ethyl]-4-methylpyridin-2-amine'>KNV</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=6nhf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nhf OCA], [http://pdbe.org/6nhf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nhf RCSB], [http://www.ebi.ac.uk/pdbsum/6nhf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nhf ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Effective delivery of therapeutic drugs into the human brain is one of the most challenging tasks in central nervous system drug development because of the blood-brain barrier (BBB). To overcome the BBB, both passive permeability and efflux transporter liability of a compound must be addressed. Herein, we report our optimization related to BBB penetration of neuronal nitric oxide synthase (nNOS) inhibitors toward the development of new drugs for neurodegenerative diseases. Various approaches, including enhancing lipophilicity and rigidity of new inhibitors and modulating the p Ka of amino groups, have been employed. In addition to determining inhibitor potency and selectivity, crystal structures of most newly designed compounds complexed to various nitric oxide synthase isoforms have been determined. We have discovered a new analogue (21), which exhibits not only excellent potency ( Ki < 30 nM) in nNOS inhibition but also a significantly low P-glycoprotein and breast-cancer-resistant protein substrate liability as indicated by an efflux ratio of 0.8 in the Caco-2 bidirectional assay.

-	~~Authors: Chreifi, G~~., Li, H., Poulos, T.L.	+	Optimization of Blood-Brain Barrier Permeability with Potent and Selective Human Neuronal Nitric Oxide Synthase Inhibitors Having a 2-Aminopyridine Scaffold.,Do HT, Li H, Chreifi G, Poulos TL, Silverman RB J Med Chem. 2019 Feb 25. doi: 10.1021/acs.jmedchem.8b02032. PMID:30802056<ref>PMID:30802056</ref>

-	~~Description: Structure~~ of ~~human endothelial nitric oxide synthase heme domain in complex with (~~S)-6-~~(2,3-difluoro-5-(2-(1-methylazetidin-2-yl)ethyl)phenethyl)-4-methylpyridin-2-amine~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	~~[[Category: Li, H~~]]	+	<div class="pdbe-citations 6nhf" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Chreifi, G]]		[[Category: Chreifi, G]]
-	[[Category: Poulos, T.L]]	+	[[Category: Li, H]]
		+	[[Category: Poulos, T L]]
		+	[[Category: Nitric oxide synthase inhibitor complex heme enzyme]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

OCA at 06:31, 30 January 2019

2019-01-30T06:31:08Z

←Older revision		Revision as of 06:31, 30 January 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

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

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

2019-01-02T04:57:15Z

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

←Older revision

Revision as of 04:57, 2 January 2019

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

2019-01-02T04:57:13Z

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

New page

'''Unreleased structure'''

The entry 6nhf is ON HOLD

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

Description: Structure of human endothelial nitric oxide synthase heme domain in complex with (S)-6-(2,3-difluoro-5-(2-(1-methylazetidin-2-yl)ethyl)phenethyl)-4-methylpyridin-2-amine
[[Category: Unreleased Structures]]
[[Category: Li, H]]
[[Category: Chreifi, G]]
[[Category: Poulos, T.L]]