5vuy - Revision history

OCA at 13:59, 4 October 2023

OCA — Wed, 04 Oct 2023 13:59:04 GMT

←Older revision		Revision as of 13:59, 4 October 2023
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	<StructureSection load='5vuy' size='340' side='right'caption='[[5vuy]], [[Resolution\|resolution]] 2.15Å' scene=''>		<StructureSection load='5vuy' size='340' side='right'caption='[[5vuy]], [[Resolution\|resolution]] 2.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5vuy]] is a 2 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=5VUY OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5VUY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5vuy]] is a 2 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=5VUY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VUY FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=P64:7-[({2-[4-(dimethylamino)phenyl]ethyl}amino)methyl]quinolin-2-amine'>P64</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]] 2.154Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5vv5\|5vv5]], [[5vv2\|5vv2]], [[5vv4\|5vv4]], [[5vuv\|5vuv]], [[5vuz\|5vuz]], [[5vv1\|5vv1]], [[5vuw\|5vuw]], [[5vux\|5vux]], [[5vv3\|5vv3]], [[5vvb\|5vvb]]</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=P64:7-[({2-[4-(dimethylamino)phenyl]ethyl}amino)methyl]quinolin-2-amine'>P64</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 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5vuy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vuy OCA], [https://pdbe.org/5vuy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vuy RCSB], [https://www.ebi.ac.uk/pdbsum/5vuy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vuy 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=5vuy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vuy OCA], [~~http~~://pdbe.org/5vuy PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5vuy RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5vuy PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5vuy ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/NOS1_HUMAN NOS1_HUMAN]] 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. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR.	+	[https://www.uniprot.org/uniprot/NOS1_HUMAN NOS1_HUMAN] 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. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR.
	<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: Li, H]]	+	[[Category: Li H]]
-	[[Category: Poulos~~, T L]]~~	+	[[Category: Poulos TL]]
-	~~[[Category: Heme enzyme]]~~	+
-	~~[[Category: Nitric oxide synthase inhibitor complex]]~~	+
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex~~]]	+

OCA at 12:38, 25 December 2019

OCA — Wed, 25 Dec 2019 12:38:05 GMT

←Older revision		Revision as of 12:38, 25 December 2019
Line 1:		Line 1:

	==Structure of human neuronal nitric oxide synthase heme domain in complex with 7-(((4-(Dimethylamino)phenethyl)amino)methyl)quinolin-2-amine==		==Structure of human neuronal nitric oxide synthase heme domain in complex with 7-(((4-(Dimethylamino)phenethyl)amino)methyl)quinolin-2-amine==
-	<StructureSection load='5vuy' size='340' side='right' caption='[[5vuy]], [[Resolution\|resolution]] 2.15Å' scene=''>	+	<StructureSection load='5vuy' size='340' side='right'caption='[[5vuy]], [[Resolution\|resolution]] 2.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5vuy]] is a 2 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=5VUY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VUY FirstGlance]. <br>		<table><tr><td colspan='2'>[[5vuy]] is a 2 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=5VUY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VUY FirstGlance]. <br>
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	</div>		</div>
	<div class="pdbe-citations 5vuy" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5vuy" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Nitric Oxide Synthase 3D structures\|Nitric Oxide Synthase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 26:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Li, H]]		[[Category: Li, H]]
	[[Category: Poulos, T L]]		[[Category: Poulos, T L]]

OCA at 20:08, 15 November 2017

OCA — Wed, 15 Nov 2017 20:08:00 GMT

←Older revision		Revision as of 20:08, 15 November 2017
Line 3:		Line 3:
	<StructureSection load='5vuy' size='340' side='right' caption='[[5vuy]], [[Resolution\|resolution]] 2.15Å' scene=''>		<StructureSection load='5vuy' size='340' side='right' caption='[[5vuy]], [[Resolution\|resolution]] 2.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5vuy]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VUY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VUY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5vuy]] is a 2 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=5VUY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VUY FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=P64:7-[({2-[4-(dimethylamino)phenyl]ethyl}amino)methyl]quinolin-2-amine'>P64</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=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=P64:7-[({2-[4-(dimethylamino)phenyl]ethyl}amino)methyl]quinolin-2-amine'>P64</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">[[5vv5\|5vv5]], [[5vv2\|5vv2]], [[5vv4\|5vv4]], [[5vuv\|5vuv]], [[5vuz\|5vuz]], [[5vv1\|5vv1]], [[5vuw\|5vuw]], [[5vux\|5vux]], [[5vv3\|5vv3]], [[5vvb\|5vvb]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5vv5\|5vv5]], [[5vv2\|5vv2]], [[5vv4\|5vv4]], [[5vuv\|5vuv]], [[5vuz\|5vuz]], [[5vv1\|5vv1]], [[5vuw\|5vuw]], [[5vux\|5vux]], [[5vv3\|5vv3]], [[5vvb\|5vvb]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NOS1 ([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='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=5vuy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vuy OCA], [http://pdbe.org/5vuy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vuy RCSB], [http://www.ebi.ac.uk/pdbsum/5vuy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vuy 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=5vuy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vuy OCA], [http://pdbe.org/5vuy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vuy RCSB], [http://www.ebi.ac.uk/pdbsum/5vuy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vuy ProSAT]</span></td></tr>
Line 24:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Li, H]]		[[Category: Li, H]]
	[[Category: Poulos, T L]]		[[Category: Poulos, T L]]

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

OCA — Thu, 17 Aug 2017 05:55:28 GMT

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

←Older revision

Revision as of 05:55, 17 August 2017

OCA: New page: ==Structure of human neuronal nitric oxide synthase heme domain in complex with 7-(((4-(Dimethylamino)phenethyl)amino)methyl)quinolin-2-amine==
OCA — Thu, 17 Aug 2017 05:55:26 GMT

New page: ==Structure of human neuronal nitric oxide synthase heme domain in complex with 7-(((4-(Dimethylamino)phenethyl)amino)methyl)quinolin-2-amine== <StructureSection load='5vuy' size='340' si...

New page

==Structure of human neuronal nitric oxide synthase heme domain in complex with 7-(((4-(Dimethylamino)phenethyl)amino)methyl)quinolin-2-amine==
<StructureSection load='5vuy' size='340' side='right' caption='[[5vuy]], [[Resolution|resolution]] 2.15Å' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5vuy]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VUY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VUY FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=P64:7-[({2-[4-(dimethylamino)phenyl]ethyl}amino)methyl]quinolin-2-amine'>P64</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">[[5vv5|5vv5]], [[5vv2|5vv2]], [[5vv4|5vv4]], [[5vuv|5vuv]], [[5vuz|5vuz]], [[5vv1|5vv1]], [[5vuw|5vuw]], [[5vux|5vux]], [[5vv3|5vv3]], [[5vvb|5vvb]]</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=5vuy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vuy OCA], [http://pdbe.org/5vuy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vuy RCSB], [http://www.ebi.ac.uk/pdbsum/5vuy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vuy ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/NOS1_HUMAN NOS1_HUMAN]] 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. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR.
<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 5vuy" style="background-color:#fffaf0;"></div>
== References ==
<references/>
TOC
</StructureSection>
[[Category: Li, H]]
[[Category: Poulos, T L]]
[[Category: Heme enzyme]]
[[Category: Nitric oxide synthase inhibitor complex]]
[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]