5vun - Revision history

OCA at 13:58, 4 October 2023

OCA — Wed, 04 Oct 2023 13:58:50 GMT

←Older revision		Revision as of 13:58, 4 October 2023
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	<StructureSection load='5vun' size='340' side='right'caption='[[5vun]], [[Resolution\|resolution]] 1.75Å' scene=''>		<StructureSection load='5vun' size='340' side='right'caption='[[5vun]], [[Resolution\|resolution]] 1.75Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5vun]] 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=5VUN OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5VUN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5vun]] 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=5VUN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VUN FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9OM:7-({[3-(4-methylpyridin-3-yl)propyl]amino}methyl)quinolin-2-amine'>9OM</scene>, <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=MTL:D-MANNITOL'>MTL</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]] 1.745Å</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=9OM:7-({[3-(4-methylpyridin-3-yl)propyl]amino}methyl)quinolin-2-amine'>9OM</scene>, <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=MTL:D-MANNITOL'>MTL</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=5vun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vun OCA], [https://pdbe.org/5vun PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vun RCSB], [https://www.ebi.ac.uk/pdbsum/5vun PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vun 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=5vun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vun OCA], [~~http~~://pdbe.org/5vun PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5vun RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5vun PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5vun 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 ==
Line 27:		Line 26:
	__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: ~~Heme enzyme]]~~	+	[[Category: Poulos TL]]
-	~~[[Category: Inhibitor complex]]~~	+
-	~~[[Category: Nitric oxide synthase]]~~	+
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex~~]]	+

OCA at 09:40, 1 January 2020

OCA — Wed, 01 Jan 2020 09:40:28 GMT

←Older revision		Revision as of 09:40, 1 January 2020
Line 1:		Line 1:

	==Structure of rat neuronal nitric oxide synthase heme domain in complex with 7-(((3-(4-Methylpyridin-3-yl)propyl)amino)methyl)quinolin-2-amine==		==Structure of rat neuronal nitric oxide synthase heme domain in complex with 7-(((3-(4-Methylpyridin-3-yl)propyl)amino)methyl)quinolin-2-amine==
-	<StructureSection load='5vun' size='340' side='right' caption='[[5vun]], [[Resolution\|resolution]] 1.75Å' scene=''>	+	<StructureSection load='5vun' size='340' side='right'caption='[[5vun]], [[Resolution\|resolution]] 1.75Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5vun]] 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=5VUN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VUN FirstGlance]. <br>		<table><tr><td colspan='2'>[[5vun]] 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=5VUN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VUN FirstGlance]. <br>
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 5vun" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5vun" 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: Buffalo rat]]		[[Category: Buffalo rat]]
		+	[[Category: Large Structures]]
	[[Category: Li, H]]		[[Category: Li, H]]
	[[Category: Poulos, T L]]		[[Category: Poulos, T L]]

OCA at 00:11, 16 November 2017

OCA — Thu, 16 Nov 2017 00:11:58 GMT

←Older revision		Revision as of 00:11, 16 November 2017
Line 3:		Line 3:
	<StructureSection load='5vun' size='340' side='right' caption='[[5vun]], [[Resolution\|resolution]] 1.75Å' scene=''>		<StructureSection load='5vun' size='340' side='right' caption='[[5vun]], [[Resolution\|resolution]] 1.75Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5vun]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VUN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VUN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5vun]] 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=5VUN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VUN FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9OM:7-({[3-(4-methylpyridin-3-yl)propyl]amino}methyl)quinolin-2-amine'>9OM</scene>, <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=MTL:D-MANNITOL'>MTL</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=9OM:7-({[3-(4-methylpyridin-3-yl)propyl]amino}methyl)quinolin-2-amine'>9OM</scene>, <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=MTL:D-MANNITOL'>MTL</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=5vun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vun OCA], [http://pdbe.org/5vun PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vun RCSB], [http://www.ebi.ac.uk/pdbsum/5vun PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vun 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=5vun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vun OCA], [http://pdbe.org/5vun PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vun RCSB], [http://www.ebi.ac.uk/pdbsum/5vun PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vun ProSAT]</span></td></tr>
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Buffalo rat]]
	[[Category: Li, H]]		[[Category: Li, H]]
	[[Category: Poulos, T L]]		[[Category: Poulos, T L]]

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

OCA — Thu, 17 Aug 2017 06:03:48 GMT

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

←Older revision

Revision as of 06:03, 17 August 2017

OCA: New page: ==Structure of rat neuronal nitric oxide synthase heme domain in complex with 7-(((3-(4-Methylpyridin-3-yl)propyl)amino)methyl)quinolin-2-amine==
OCA — Thu, 17 Aug 2017 06:03:46 GMT

New page: ==Structure of rat neuronal nitric oxide synthase heme domain in complex with 7-(((3-(4-Methylpyridin-3-yl)propyl)amino)methyl)quinolin-2-amine== <StructureSection load='5vun' size='340' ...

New page

==Structure of rat neuronal nitric oxide synthase heme domain in complex with 7-(((3-(4-Methylpyridin-3-yl)propyl)amino)methyl)quinolin-2-amine==
<StructureSection load='5vun' size='340' side='right' caption='[[5vun]], [[Resolution|resolution]] 1.75Å' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5vun]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VUN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VUN FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9OM:7-({[3-(4-methylpyridin-3-yl)propyl]amino}methyl)quinolin-2-amine'>9OM</scene>, <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=MTL:D-MANNITOL'>MTL</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=5vun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vun OCA], [http://pdbe.org/5vun PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vun RCSB], [http://www.ebi.ac.uk/pdbsum/5vun PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vun 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 ==
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 5vun" 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]]