6ngu - Revision history

OCA at 06:53, 11 October 2023

OCA — Wed, 11 Oct 2023 06:53:33 GMT

←Older revision		Revision as of 06:53, 11 October 2023
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	<StructureSection load='6ngu' size='340' side='right'caption='[[6ngu]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='6ngu' size='340' side='right'caption='[[6ngu]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ngu]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Buffalo_rat Buffalo rat~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NGU OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6NGU FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ngu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NGU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NGU FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</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=KMJ:6-(2-{3-[3-(dimethylamino)propyl]-2,5-difluorophenyl}ethyl)-4-methylpyridin-2-amine'>KMJ</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]] 2Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Nos1, Bnos ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</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=KMJ:6-(2-{3-[3-(dimethylamino)propyl]-2,5-difluorophenyl}ethyl)-4-methylpyridin-2-amine'>KMJ</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=6ngu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ngu OCA], [https://pdbe.org/6ngu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ngu RCSB], [https://www.ebi.ac.uk/pdbsum/6ngu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ngu 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=6ngu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ngu OCA], [~~http~~://pdbe.org/6ngu PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6ngu RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6ngu PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6ngu ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/NOS1_RAT NOS1_RAT]] Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum.	+	[https://www.uniprot.org/uniprot/NOS1_RAT NOS1_RAT] Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum.
	<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: Buffalo rat]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Li, H~~]]	+	[[Category: Rattus norvegicus]]
-	[[Category: ~~Poulos, T L~~]]	+	[[Category: Li H]]
-	[[Category: ~~Nitric oxide synthase inhibitor complex heme enzyme]]~~	+	[[Category: Poulos TL]]
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex~~]]	+

OCA at 10:33, 4 December 2019

OCA — Wed, 04 Dec 2019 10:33:19 GMT

←Older revision		Revision as of 10:33, 4 December 2019
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	</div>		</div>
	<div class="pdbe-citations 6ngu" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6ngu" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Nitric Oxide Synthase 3D structures\|Nitric Oxide Synthase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:11, 27 March 2019

OCA — Wed, 27 Mar 2019 07:11:28 GMT

←Older revision		Revision as of 07:11, 27 March 2019
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	<StructureSection load='6ngu' size='340' side='right'caption='[[6ngu]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='6ngu' size='340' side='right'caption='[[6ngu]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ngu]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NGU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NGU FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ngu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NGU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NGU FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</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=KMJ:6-(2-{3-[3-(dimethylamino)propyl]-2,5-difluorophenyl}ethyl)-4-methylpyridin-2-amine'>KMJ</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=ACT:ACETATE+ION'>ACT</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=KMJ:6-(2-{3-[3-(dimethylamino)propyl]-2,5-difluorophenyl}ethyl)-4-methylpyridin-2-amine'>KMJ</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">Nos1, Bnos ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=6ngu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ngu OCA], [http://pdbe.org/6ngu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ngu RCSB], [http://www.ebi.ac.uk/pdbsum/6ngu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ngu 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=6ngu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ngu OCA], [http://pdbe.org/6ngu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ngu RCSB], [http://www.ebi.ac.uk/pdbsum/6ngu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ngu ProSAT]</span></td></tr>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Buffalo rat]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Li, H]]		[[Category: Li, H]]

OCA at 12:20, 13 March 2019

OCA — Wed, 13 Mar 2019 12:20:25 GMT

←Older revision		Revision as of 12:20, 13 March 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6ngu is ~~ON HOLD until Paper~~ Publication	+	==Structure of rat neuronal nitric oxide synthase heme domain in complex with 6-(3-(3-(dimethylamino)propyl)-2,5-difluorophenethyl)-4-methylpyridin-2-amine==
		+	<StructureSection load='6ngu' size='340' side='right'caption='[[6ngu]], [[Resolution\|resolution]] 2.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6ngu]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NGU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NGU FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</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=KMJ:6-(2-{3-[3-(dimethylamino)propyl]-2,5-difluorophenyl}ethyl)-4-methylpyridin-2-amine'>KMJ</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ngu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ngu OCA], [http://pdbe.org/6ngu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ngu RCSB], [http://www.ebi.ac.uk/pdbsum/6ngu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ngu ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/NOS1_RAT NOS1_RAT]] Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum.
		+	<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: 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 ~~rat neuronal nitric oxide synthase heme domain in complex with 6~~-(3-~~(3-(dimethylamino)propyl)-2,5-difluorophenethyl)-4-methylpyridin-2-amine~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6ngu" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Li, H]]		[[Category: Li, H]]
-	[[Category: Poulos, T.L]]	+	[[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

OCA — Wed, 30 Jan 2019 06:31:05 GMT

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

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

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

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

OCA — Wed, 02 Jan 2019 04:56:07 GMT

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

←Older revision

Revision as of 04:56, 2 January 2019

OCA: New page: '''Unreleased structure''' The entry 6ngu is ON HOLD Authors: Li, H., Poulos, T.L. Description: Structure of rat neuronal nitric oxide synthase heme domain in complex with 6-(3-(3-(dim...

OCA — Wed, 02 Jan 2019 04:56:05 GMT

New page: '''Unreleased structure''' The entry 6ngu is ON HOLD Authors: Li, H., Poulos, T.L. Description: Structure of rat neuronal nitric oxide synthase heme domain in complex with 6-(3-(3-(dim...

New page

'''Unreleased structure'''

The entry 6ngu is ON HOLD

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

Description: Structure of rat neuronal nitric oxide synthase heme domain in complex with 6-(3-(3-(dimethylamino)propyl)-2,5-difluorophenethyl)-4-methylpyridin-2-amine
[[Category: Unreleased Structures]]
[[Category: Li, H]]
[[Category: Poulos, T.L]]