4cap - Revision history

OCA at 11:10, 9 May 2024

2024-05-09T11:10:36Z

← Older revision		Revision as of 11:10, 9 May 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4cap]] 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=4CAP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CAP FirstGlance]. <br>		<table><tr><td colspan='2'>[[4cap]] 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=4CAP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CAP FirstGlance]. <br>
	</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=ML6:7-({[3-(3-FLUOROPHENYL)PROPYL]AMINO}METHYL)QUINOLIN-2-AMINE'>ML6</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]] 2.06Å</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=ML6:7-({[3-(3-FLUOROPHENYL)PROPYL]AMINO}METHYL)QUINOLIN-2-AMINE'>ML6</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=4cap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cap OCA], [https://pdbe.org/4cap PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cap RCSB], [https://www.ebi.ac.uk/pdbsum/4cap PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cap ProSAT]</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=4cap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cap OCA], [https://pdbe.org/4cap PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cap RCSB], [https://www.ebi.ac.uk/pdbsum/4cap PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cap ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[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.		[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;">
			== Publication Abstract from PubMed ==
			Since high levels of nitric oxide (NO) are implicated in neurodegenerative disorders, inhibition of the neuronal isoform of nitric oxide synthase (nNOS) and reduction of NO levels are therapeutically desirable. Nonetheless, many nNOS inhibitors mimic l-arginine and are poorly bioavailable. 2-Aminoquinoline-based scaffolds were designed with the hope that they could (a) mimic aminopyridines as potent, isoform-selective arginine isosteres and (b) possess chemical properties more conducive to oral bioavailability and CNS penetration. A series of these compounds was synthesized and assayed against purified nNOS enzymes, endothelial NOS (eNOS), and inducible NOS (iNOS). Several compounds built on a 7-substituted 2-aminoquinoline core are potent and isoform-selective; X-ray crystallography indicates that aminoquinolines exert inhibitory effects by mimicking substrate interactions with the conserved active site glutamate residue. The most potent and selective compounds, 7 and 15, were tested in a Caco-2 assay and showed good permeability and low efflux, suggesting high potential for oral bioavailability.

			Simplified 2-Aminoquinoline-Based Scaffold for Potent and Selective Neuronal Nitric Oxide Synthase Inhibition.,Cinelli MA, Li H, Chreifi G, Martasek P, Roman LJ, Poulos TL, Silverman RB J Med Chem. 2014 Feb 10. PMID:24472039<ref>PMID:24472039</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 4cap" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Nitric Oxide Synthase 3D structures\|Nitric Oxide Synthase 3D structures]]		*[[Nitric Oxide Synthase 3D structures\|Nitric Oxide Synthase 3D structures]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 17:35, 7 September 2022

2022-09-07T17:35:03Z

← Older revision		Revision as of 17:35, 7 September 2022
Line 3:		Line 3:
	<StructureSection load='4cap' size='340' side='right'caption='[[4cap]], [[Resolution\|resolution]] 2.06Å' scene=''>		<StructureSection load='4cap' size='340' side='right'caption='[[4cap]], [[Resolution\|resolution]] 2.06Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4cap]] 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=4CAP OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4CAP FirstGlance]. <br>		<table><tr><td colspan='2'>[[4cap]] 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=4CAP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CAP 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=ML6:7-({[3-(3-FLUOROPHENYL)PROPYL]AMINO}METHYL)QUINOLIN-2-AMINE'>ML6</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=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=ML6:7-({[3-(3-FLUOROPHENYL)PROPYL]AMINO}METHYL)QUINOLIN-2-AMINE'>ML6</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4cam\|4cam]], [[4can\|4can]], [[4cao\|4cao]], [[4caq\|4caq]], [[4car\|4car]], [[4cdt\|4cdt]], [[4cft\|4cft]]</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=4cap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cap OCA], [https://pdbe.org/4cap PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cap RCSB], [https://www.ebi.ac.uk/pdbsum/4cap PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cap 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=4cap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cap OCA], [~~http~~://pdbe.org/4cap PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4cap RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4cap PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4cap 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;">~~
	~~== Publication Abstract from PubMed ==~~
	Since high levels of nitric oxide (NO) are implicated in neurodegenerative disorders, inhibition of the neuronal isoform of nitric oxide synthase (nNOS) and reduction of NO levels are therapeutically desirable. Nonetheless, many nNOS inhibitors mimic l-arginine and are poorly bioavailable. 2-Aminoquinoline-based scaffolds were designed with the hope that they could (a) mimic aminopyridines as potent, isoform-selective arginine isosteres and (b) possess chemical properties more conducive to oral bioavailability and CNS penetration. A series of these compounds was synthesized and assayed against purified nNOS enzymes, endothelial NOS (eNOS), and inducible NOS (iNOS). Several compounds built on a 7-substituted 2-aminoquinoline core are potent and isoform-selective; X-ray crystallography indicates that aminoquinolines exert inhibitory effects by mimicking substrate interactions with the conserved active site glutamate residue. The most potent and selective compounds, 7 and 15, were tested in a Caco-2 assay and showed good permeability and low efflux, suggesting high potential for oral bioavailability.

	Simplified 2-Aminoquinoline-Based Scaffold for Potent and Selective Neuronal Nitric Oxide Synthase Inhibition.,Cinelli MA, Li H, Chreifi G, Martasek P, Roman LJ, Poulos TL, Silverman RB J Med Chem. 2014 Feb 10. PMID:24472039<ref>PMID:24472039</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4cap" style="background-color:#fffaf0;"></div>~~

	==See Also==		==See Also==
	*[[Nitric Oxide Synthase\|Nitric Oxide Synthase]]		*[[Nitric Oxide Synthase 3D structures\|Nitric Oxide Synthase 3D structures]]
	~~== References ==~~
	~~<references/>~~
	__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: ~~Inhibitor complex]]~~		[[Category: Poulos TL]]
	~~[[Category: Nitric oxide synthase]]~~
	~~[[Category: Oxidoreductase~~]]

OCA at 16:43, 28 August 2019

2019-08-28T16:43:13Z

← Older revision		Revision as of 16:43, 28 August 2019
Line 1:		Line 1:

	==Structure of rat neuronal nitric oxide synthase heme domain in complex with 7-(2-(3-(3-Fluorophenyl(propylamino)methyl))quinolin-2- amine==		==Structure of rat neuronal nitric oxide synthase heme domain in complex with 7-(2-(3-(3-Fluorophenyl(propylamino)methyl))quinolin-2- amine==
	<StructureSection load='4cap' size='340' side='right' caption='[[4cap]], [[Resolution\|resolution]] 2.06Å' scene=''>		<StructureSection load='4cap' size='340' side='right'caption='[[4cap]], [[Resolution\|resolution]] 2.06Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4cap]] 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=4CAP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CAP FirstGlance]. <br>		<table><tr><td colspan='2'>[[4cap]] 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=4CAP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CAP FirstGlance]. <br>
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 4cap" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4cap" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Nitric Oxide Synthase\|Nitric Oxide Synthase]]
	== References ==		== References ==
	<references/>		<references/>
Line 25:		Line 28:
	</StructureSection>		</StructureSection>
	[[Category: Buffalo rat]]		[[Category: Buffalo rat]]
			[[Category: Large Structures]]
	[[Category: Li, H]]		[[Category: Li, H]]
	[[Category: Poulos, T L]]		[[Category: Poulos, T L]]

OCA at 14:48, 15 November 2017

2017-11-15T14:48:40Z

← Older revision		Revision as of 14:48, 15 November 2017
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 4cap" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4cap" style="background-color:#fffaf0;"></div>

	~~==See Also==~~
	*[[Nitric Oxide Synthase\|Nitric Oxide Synthase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 17:34, 4 August 2016

2016-08-04T17:34:00Z

← Older revision		Revision as of 17:34, 4 August 2016
Line 1:		Line 1:

	==Structure of rat neuronal nitric oxide synthase heme domain in complex with 7-(2-(3-(3-Fluorophenyl(propylamino)methyl))quinolin-2- amine==		==Structure of rat neuronal nitric oxide synthase heme domain in complex with 7-(2-(3-(3-Fluorophenyl(propylamino)methyl))quinolin-2- amine==
	<StructureSection load='4cap' size='340' side='right' caption='[[4cap]], [[Resolution\|resolution]] 2.06Å' scene=''>		<StructureSection load='4cap' size='340' side='right' caption='[[4cap]], [[Resolution\|resolution]] 2.06Å' scene=''>
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	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4cam\|4cam]], [[4can\|4can]], [[4cao\|4cao]], [[4caq\|4caq]], [[4car\|4car]], [[4cdt\|4cdt]], [[4cft\|4cft]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4cam\|4cam]], [[4can\|4can]], [[4cao\|4cao]], [[4caq\|4caq]], [[4car\|4car]], [[4cdt\|4cdt]], [[4cft\|4cft]]</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=4cap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cap OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4cap RCSB], [http://www.ebi.ac.uk/pdbsum/4cap 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=4cap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cap OCA], [http://pdbe.org/4cap PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cap RCSB], [http://www.ebi.ac.uk/pdbsum/4cap PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cap ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 4cap" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 11:27, 25 December 2014

2014-12-25T11:27:05Z

← Older revision		Revision as of 11:27, 25 December 2014
Line 8:		Line 8:
	<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=4cap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cap OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4cap RCSB], [http://www.ebi.ac.uk/pdbsum/4cap 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=4cap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cap OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4cap RCSB], [http://www.ebi.ac.uk/pdbsum/4cap PDBsum]</span></td></tr>
	</table>		</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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 17:11, 21 December 2014

2014-12-21T17:11:29Z

← Older revision		Revision as of 17:11, 21 December 2014
Line 1:		Line 1:
	~~{{STRUCTURE_4cap\| PDB=4cap \| SCENE= }}~~		==Structure of rat neuronal nitric oxide synthase heme domain in complex with 7-(2-(3-(3-Fluorophenyl(propylamino)methyl))quinolin-2- amine==
	===Structure of rat neuronal nitric oxide synthase heme domain in complex with 7-(2-(3-(3-Fluorophenyl(propylamino)methyl))quinolin-2- amine===		<StructureSection load='4cap' size='340' side='right' caption='[[4cap]], [[Resolution\|resolution]] 2.06Å' scene=''>
	{~~{ABSTRACT_PUBMED_24472039}~~}		== Structural highlights ==
			<table><tr><td colspan='2'>[[4cap]] 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=4CAP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CAP 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=ML6:7-({[3-(3-FLUOROPHENYL)PROPYL]AMINO}METHYL)QUINOLIN-2-AMINE'>ML6</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4cam\|4cam]], [[4can\|4can]], [[4cao\|4cao]], [[4caq\|4caq]], [[4car\|4car]], [[4cdt\|4cdt]], [[4cft\|4cft]]</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=4cap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cap OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4cap RCSB], [http://www.ebi.ac.uk/pdbsum/4cap PDBsum]</span></td></tr>
			</table>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Since high levels of nitric oxide (NO) are implicated in neurodegenerative disorders, inhibition of the neuronal isoform of nitric oxide synthase (nNOS) and reduction of NO levels are therapeutically desirable. Nonetheless, many nNOS inhibitors mimic l-arginine and are poorly bioavailable. 2-Aminoquinoline-based scaffolds were designed with the hope that they could (a) mimic aminopyridines as potent, isoform-selective arginine isosteres and (b) possess chemical properties more conducive to oral bioavailability and CNS penetration. A series of these compounds was synthesized and assayed against purified nNOS enzymes, endothelial NOS (eNOS), and inducible NOS (iNOS). Several compounds built on a 7-substituted 2-aminoquinoline core are potent and isoform-selective; X-ray crystallography indicates that aminoquinolines exert inhibitory effects by mimicking substrate interactions with the conserved active site glutamate residue. The most potent and selective compounds, 7 and 15, were tested in a Caco-2 assay and showed good permeability and low efflux, suggesting high potential for oral bioavailability.

	~~==Function==~~		Simplified 2-Aminoquinoline-Based Scaffold for Potent and Selective Neuronal Nitric Oxide Synthase Inhibition.,Cinelli MA, Li H, Chreifi G, Martasek P, Roman LJ, Poulos TL, Silverman RB J Med Chem. 2014 Feb 10. PMID:24472039<ref>PMID:24472039</ref>
	[[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~~.

	~~==About this Structure==~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[4cap]] is~~ a ~~2 chain structure. Full crystallographic information is available from [http://oca~~.~~weizmann~~.ac.~~il/oca-bin~~/~~ocashort?id=4CAP OCA].~~		</div>

	==~~Reference~~==		==See Also==
	~~<ref group~~=~~"xtra">PMID:024472039</ref>~~<references ~~group="xtra"~~/><~~references~~/>		*[[Nitric Oxide Synthase\|Nitric Oxide Synthase]]
	[[Category: Li, H.]]		== References ==
	[[Category: Poulos, T L.]]		<references/>
			__TOC__
			</StructureSection>
			[[Category: Buffalo rat]]
			[[Category: Li, H]]
			[[Category: Poulos, T L]]
	[[Category: Inhibitor complex]]		[[Category: Inhibitor complex]]
	[[Category: Nitric oxide synthase]]		[[Category: Nitric oxide synthase]]
	[[Category: Oxidoreductase]]		[[Category: Oxidoreductase]]

OCA at 17:27, 19 February 2014

2014-02-19T17:27:36Z

← Older revision		Revision as of 17:27, 19 February 2014
Line 1:		Line 1:
	~~'''Unreleased structure'''~~		{{STRUCTURE_4cap\| PDB=4cap \| SCENE= }}
			===Structure of rat neuronal nitric oxide synthase heme domain in complex with 7-(2-(3-(3-Fluorophenyl(propylamino)methyl))quinolin-2- amine===
			{{ABSTRACT_PUBMED_24472039}}

	~~The entry 4cap~~ is ~~ON HOLD until Paper Publication~~		==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.

	~~Authors~~: ~~Li, H~~.~~, Poulos, T~~.L.		==About this Structure==
			[[4cap]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CAP OCA].

	~~Description~~: ~~Structure of rat neuronal nitric~~ oxide synthase ~~heme domain in complex with 7-(2-(3-(3-Fluorophenyl(propylamino)methyl))quinolin-2-amine~~		==Reference==
			<ref group="xtra">PMID:024472039</ref><references group="xtra"/><references/>
			[[Category: Li, H.]]
			[[Category: Poulos, T L.]]
			[[Category: Inhibitor complex]]
			[[Category: Nitric oxide synthase]]
			[[Category: Oxidoreductase]]

OCA at 05:39, 23 October 2013

2013-10-23T05:39:13Z

← Older revision		Revision as of 05:39, 23 October 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 4cap is ON HOLD		The entry 4cap is ON HOLD until Paper Publication

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

	Description: Structure of rat neuronal nitric oxide synthase heme domain in complex with 7-(2-(3-(3-Fluorophenyl(propylamino)methyl))quinolin-2-amine		Description: Structure of rat neuronal nitric oxide synthase heme domain in complex with 7-(2-(3-(3-Fluorophenyl(propylamino)methyl))quinolin-2-amine

OCA: Protected "4cap" [edit=sysop:move=sysop]

2013-10-16T07:09:40Z

Protected "4cap" [edit=sysop:move=sysop]

← Older revision	Revision as of 07:09, 16 October 2013
(No difference)