3ufq - Revision history

OCA at 13:56, 14 March 2024

2024-03-14T13:56:49Z

←Older revision		Revision as of 13:56, 14 March 2024
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	<StructureSection load='3ufq' size='340' side='right'caption='[[3ufq]], [[Resolution\|resolution]] 2.06Å' scene=''>		<StructureSection load='3ufq' size='340' side='right'caption='[[3ufq]], [[Resolution\|resolution]] 2.06Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3ufq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Buffalo_rat Buffalo rat~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UFQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UFQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3ufq]] 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=3UFQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UFQ 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=HW5:6-{[(3S,4S)-4-{[(4E)-5-(3-FLUOROPHENYL)PENT-4-EN-1-YL]OXY}PYRROLIDIN-3-YL]METHYL}-4-METHYLPYRIDIN-2-AMINE'>HW5</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]] 2.058Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ufo\|3ufo]], [[3ufp\|3ufp]], [[3ufr\|3ufr]], [[3ufs\|3ufs]], [[3uft\|3uft]], [[3ufu\|3ufu]], [[3ufv\|3ufv]], [[3ufw\|3ufw]]</div></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=HW5:6-{[(3S,4S)-4-{[(4E)-5-(3-FLUOROPHENYL)PENT-4-EN-1-YL]OXY}PYRROLIDIN-3-YL]METHYL}-4-METHYLPYRIDIN-2-AMINE'>HW5</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 ([https://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'>[https://en.wikipedia.org/wiki/Nitric-oxide_synthase_(NADPH_dependent) Nitric-oxide synthase (NADPH dependent)], with EC number [https://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=3ufq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ufq OCA], [https://pdbe.org/3ufq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ufq RCSB], [https://www.ebi.ac.uk/pdbsum/3ufq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ufq 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=3ufq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ufq OCA], [https://pdbe.org/3ufq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ufq RCSB], [https://www.ebi.ac.uk/pdbsum/3ufq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ufq 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 ==~~	+
-	The reduction of pathophysiologic levels of nitric oxide through inhibition of neuronal nitric oxide synthase (nNOS) has the potential to be therapeutically beneficial in various neurodegenerative diseases. We have developed a series of pyrrolidine-based nNOS inhibitors that exhibit excellent potencies and isoform selectivities (J. Am. Chem. Soc. 2010, 132, 5437). However, there are still important challenges, such as how to decrease the multiple positive charges derived from basic amino groups, which contribute to poor bioavailability, without losing potency and/or selectivity. Here we present an interdisciplinary study combining molecular docking, crystallography, molecular dynamics simulations, synthesis, and enzymology to explore potential pharmacophoric features of nNOS inhibitors and to design potent and selective monocationic nNOS inhibitors. The simulation results indicate that different hydrogen bond patterns, electrostatic interactions, hydrophobic interactions, and a water molecule bridge are key factors for stabilizing ligands and controlling ligand orientation. We find that a heteroatom in the aromatic head or linker chain of the ligand provides additional stability and blocks the substrate binding pocket. Finally, the computational insights are experimentally validated with double-headed pyridine analogs. The compounds reported here are among the most potent and selective monocationic pyrrolidine-based nNOS inhibitors reported to date, and 10 shows improved membrane permeability.	+
-		+
-	Selective Monocationic Inhibitors of Neuronal Nitric Oxide Synthase. Binding Mode Insights from Molecular Dynamics Simulations.,Huang H, Ji H, Li H, Jing Q, Jansen Labby K, Martasek P, Roman LJ, Poulos TL, Silverman RB J Am Chem Soc. 2012 Jun 25. PMID:22731813<ref>PMID:22731813</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3ufq" 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>
-	[[Category: Buffalo rat]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Li, H~~]]	+	[[Category: Rattus norvegicus]]
-	[[Category: ~~Poulos, T L~~]]	+	[[Category: Li H]]
-	[[Category: ~~Inhibitor binding]]~~	+	[[Category: Poulos TL]]
-	~~[[Category: Nitric oxide synthase]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex~~]]	+

OCA at 06:11, 13 July 2022

2022-07-13T06:11:24Z

←Older revision		Revision as of 06:11, 13 July 2022
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	==Structure of rat nitric oxide synthase heme domain in complex with 6-(((3S,4S)-4-(((E)-5-(3-fluorophenyl)pent-4-en-1-yl)oxy)pyrrolidin-3-yl)methyl)-4-methylpyridin-2-amine==		==Structure of rat nitric oxide synthase heme domain in complex with 6-(((3S,4S)-4-(((E)-5-(3-fluorophenyl)pent-4-en-1-yl)oxy)pyrrolidin-3-yl)methyl)-4-methylpyridin-2-amine==
-	<StructureSection load='3ufq' size='340' side='right' caption='[[3ufq]], [[Resolution\|resolution]] 2.06Å' scene=''>	+	<StructureSection load='3ufq' size='340' side='right'caption='[[3ufq]], [[Resolution\|resolution]] 2.06Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3ufq]] 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=3UFQ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3UFQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3ufq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UFQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UFQ 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=HW5:6-{[(3S,4S)-4-{[(4E)-5-(3-FLUOROPHENYL)PENT-4-EN-1-YL]OXY}PYRROLIDIN-3-YL]METHYL}-4-METHYLPYRIDIN-2-AMINE'>HW5</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=HW5:6-{[(3S,4S)-4-{[(4E)-5-(3-FLUOROPHENYL)PENT-4-EN-1-YL]OXY}PYRROLIDIN-3-YL]METHYL}-4-METHYLPYRIDIN-2-AMINE'>HW5</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">[[3ufo\|3ufo]], [[3ufp\|3ufp]], [[3ufr\|3ufr]], [[3ufs\|3ufs]], [[3uft\|3uft]], [[3ufu\|3ufu]], [[3ufv\|3ufv]], [[3ufw\|3ufw]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ufo\|3ufo]], [[3ufp\|3ufp]], [[3ufr\|3ufr]], [[3ufs\|3ufs]], [[3uft\|3uft]], [[3ufu\|3ufu]], [[3ufv\|3ufv]], [[3ufw\|3ufw]]</div></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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Nos1, Bnos ([https://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'>[https://en.wikipedia.org/wiki/Nitric-oxide_synthase_(NADPH_dependent) Nitric-oxide synthase (NADPH dependent)], with EC number [https://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=3ufq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ufq OCA], [~~http~~://pdbe.org/3ufq PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3ufq RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3ufq PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3ufq 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=3ufq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ufq OCA], [https://pdbe.org/3ufq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ufq RCSB], [https://www.ebi.ac.uk/pdbsum/3ufq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ufq 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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	</div>		</div>
	<div class="pdbe-citations 3ufq" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3ufq" 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 10:03, 8 November 2017

2017-11-08T10:03:57Z

←Older revision		Revision as of 10:03, 8 November 2017
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	</div>		</div>
	<div class="pdbe-citations 3ufq" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3ufq" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Nitric Oxide Synthase\|Nitric Oxide Synthase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 00:27, 5 August 2016

2016-08-05T00:27:34Z

←Older revision		Revision as of 00:27, 5 August 2016
Line 1:		Line 1:
		+
	==Structure of rat nitric oxide synthase heme domain in complex with 6-(((3S,4S)-4-(((E)-5-(3-fluorophenyl)pent-4-en-1-yl)oxy)pyrrolidin-3-yl)methyl)-4-methylpyridin-2-amine==		==Structure of rat nitric oxide synthase heme domain in complex with 6-(((3S,4S)-4-(((E)-5-(3-fluorophenyl)pent-4-en-1-yl)oxy)pyrrolidin-3-yl)methyl)-4-methylpyridin-2-amine==
	<StructureSection load='3ufq' size='340' side='right' caption='[[3ufq]], [[Resolution\|resolution]] 2.06Å' scene=''>		<StructureSection load='3ufq' size='340' side='right' caption='[[3ufq]], [[Resolution\|resolution]] 2.06Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3ufq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Rattus_norvegicus Rattus norvegicus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UFQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UFQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3ufq]] 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=3UFQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UFQ 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=HW5:6-{[(3S,4S)-4-{[(4E)-5-(3-FLUOROPHENYL)PENT-4-EN-1-YL]OXY}PYRROLIDIN-3-YL]METHYL}-4-METHYLPYRIDIN-2-AMINE'>HW5</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=HW5:6-{[(3S,4S)-4-{[(4E)-5-(3-FLUOROPHENYL)PENT-4-EN-1-YL]OXY}PYRROLIDIN-3-YL]METHYL}-4-METHYLPYRIDIN-2-AMINE'>HW5</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">[[3ufo\|3ufo]], [[3ufp\|3ufp]], [[3ufr\|3ufr]], [[3ufs\|3ufs]], [[3uft\|3uft]], [[3ufu\|3ufu]], [[3ufv\|3ufv]], [[3ufw\|3ufw]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ufo\|3ufo]], [[3ufp\|3ufp]], [[3ufr\|3ufr]], [[3ufs\|3ufs]], [[3uft\|3uft]], [[3ufu\|3ufu]], [[3ufv\|3ufv]], [[3ufw\|3ufw]]</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 ~~Rattus norvegicus~~])</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~~ Nitric-oxide synthase], 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=3ufq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ufq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ufq RCSB], [http://www.ebi.ac.uk/pdbsum/3ufq 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=3ufq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ufq OCA], [http://pdbe.org/3ufq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ufq RCSB], [http://www.ebi.ac.uk/pdbsum/3ufq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ufq ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
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	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 3ufq" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 26:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Nitric-oxide synthase]]~~	+	[[Category: Buffalo rat]]
-	~~[[Category: Rattus norvegicus~~]]	+
	[[Category: Li, H]]		[[Category: Li, H]]
	[[Category: Poulos, T L]]		[[Category: Poulos, T L]]

OCA at 14:21, 25 December 2014

2014-12-25T14:21:52Z

←Older revision		Revision as of 14:21, 25 December 2014
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	<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=3ufq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ufq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ufq RCSB], [http://www.ebi.ac.uk/pdbsum/3ufq 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=3ufq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ufq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ufq RCSB], [http://www.ebi.ac.uk/pdbsum/3ufq 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 15:23, 9 December 2014

2014-12-09T15:23:04Z

←Older revision		Revision as of 15:23, 9 December 2014
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-	[[~~Image:~~3ufq.~~png~~\|~~left~~\|~~200px~~]]	+	==Structure of rat nitric oxide synthase heme domain in complex with 6-(((3S,4S)-4-(((E)-5-(3-fluorophenyl)pent-4-en-1-yl)oxy)pyrrolidin-3-yl)methyl)-4-methylpyridin-2-amine==
		+	<StructureSection load='3ufq' size='340' side='right' caption='[[3ufq]], [[Resolution\|resolution]] 2.06Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3ufq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UFQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UFQ 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=HW5:6-{[(3S,4S)-4-{[(4E)-5-(3-FLUOROPHENYL)PENT-4-EN-1-YL]OXY}PYRROLIDIN-3-YL]METHYL}-4-METHYLPYRIDIN-2-AMINE'>HW5</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">[[3ufo\|3ufo]], [[3ufp\|3ufp]], [[3ufr\|3ufr]], [[3ufs\|3ufs]], [[3uft\|3uft]], [[3ufu\|3ufu]], [[3ufv\|3ufv]], [[3ufw\|3ufw]]</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 Rattus norvegicus])</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 Nitric-oxide synthase], 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=3ufq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ufq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ufq RCSB], [http://www.ebi.ac.uk/pdbsum/3ufq PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The reduction of pathophysiologic levels of nitric oxide through inhibition of neuronal nitric oxide synthase (nNOS) has the potential to be therapeutically beneficial in various neurodegenerative diseases. We have developed a series of pyrrolidine-based nNOS inhibitors that exhibit excellent potencies and isoform selectivities (J. Am. Chem. Soc. 2010, 132, 5437). However, there are still important challenges, such as how to decrease the multiple positive charges derived from basic amino groups, which contribute to poor bioavailability, without losing potency and/or selectivity. Here we present an interdisciplinary study combining molecular docking, crystallography, molecular dynamics simulations, synthesis, and enzymology to explore potential pharmacophoric features of nNOS inhibitors and to design potent and selective monocationic nNOS inhibitors. The simulation results indicate that different hydrogen bond patterns, electrostatic interactions, hydrophobic interactions, and a water molecule bridge are key factors for stabilizing ligands and controlling ligand orientation. We find that a heteroatom in the aromatic head or linker chain of the ligand provides additional stability and blocks the substrate binding pocket. Finally, the computational insights are experimentally validated with double-headed pyridine analogs. The compounds reported here are among the most potent and selective monocationic pyrrolidine-based nNOS inhibitors reported to date, and 10 shows improved membrane permeability.

-	~~{{STRUCTURE_3ufq\| PDB=3ufq \| SCENE= }}~~	+	Selective Monocationic Inhibitors of Neuronal Nitric Oxide Synthase. Binding Mode Insights from Molecular Dynamics Simulations.,Huang H, Ji H, Li H, Jing Q, Jansen Labby K, Martasek P, Roman LJ, Poulos TL, Silverman RB J Am Chem Soc. 2012 Jun 25. PMID:22731813<ref>PMID:22731813</ref>

-	~~===Structure of rat nitric oxide synthase heme domain in complex with 6-(((3S~~,~~4S)-4-(((E)-5-(3-fluorophenyl)pent-4-en-1-yl)oxy)pyrrolidin-3-yl)methyl)-4-methylpyridin-2-amine===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

-	~~{{ABSTRACT_PUBMED_22731813}}~~	+	==See Also==
-		+	*[[Nitric Oxide Synthase\|Nitric Oxide Synthase]]
-	==~~About this Structure~~==	+	== References ==
-	[[~~3ufq~~]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UFQ OCA].	+	<references/>
-		+	__TOC__
-	==~~Reference~~==	+	</StructureSection>
-	<~~ref group="xtra">PMID:022731813<~~/~~ref~~><~~references group="xtra"~~/>	+
	[[Category: Nitric-oxide synthase]]		[[Category: Nitric-oxide synthase]]
	[[Category: Rattus norvegicus]]		[[Category: Rattus norvegicus]]
-	[[Category: Li, H.]]	+	[[Category: Li, H]]
-	[[Category: Poulos, T L.]]	+	[[Category: Poulos, T L]]
	[[Category: Inhibitor binding]]		[[Category: Inhibitor binding]]
	[[Category: Nitric oxide synthase]]		[[Category: Nitric oxide synthase]]
	[[Category: Oxidoreductase]]		[[Category: Oxidoreductase]]
	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]		[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

OCA at 05:06, 1 August 2012

2012-08-01T05:06:28Z

←Older revision		Revision as of 05:06, 1 August 2012
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-	[[Image:3ufq.~~jpg~~\|left\|200px]]	+	[[Image:3ufq.png\|left\|200px]]

	{{STRUCTURE_3ufq\| PDB=3ufq \| SCENE= }}		{{STRUCTURE_3ufq\| PDB=3ufq \| SCENE= }}

OCA at 08:15, 11 July 2012

2012-07-11T08:15:22Z

←Older revision		Revision as of 08:15, 11 July 2012
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-	~~'''Unreleased structure'''~~	+	[[Image:3ufq.jpg\|left\|200px]]

-	~~The entry~~ 3ufq ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_3ufq\| PDB=3ufq \| SCENE= }}

-	~~Authors: Li~~, ~~H., Poulos, T.L.~~	+	===Structure of rat nitric oxide synthase heme domain in complex with 6-(((3S,4S)-4-(((E)-5-(3-fluorophenyl)pent-4-en-1-yl)oxy)pyrrolidin-3-yl)methyl)-4-methylpyridin-2-amine===

-	~~Description:~~ Structure ~~of rat nitric oxide synthase heme domain in complex~~ with ~~6-(((3S,4S)-4-(((E)-5-(3-fluorophenyl)pent-4-~~en-1-~~yl)oxy)pyrrolidin~~-~~3-yl)methyl)-4-methylpyridin-2-amine~~	+	{{ABSTRACT_PUBMED_22731813}}
		+
		+	==About this Structure==
		+	[[3ufq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UFQ OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:022731813</ref><references group="xtra"/>
		+	[[Category: Nitric-oxide synthase]]
		+	[[Category: Rattus norvegicus]]
		+	[[Category: Li, H.]]
		+	[[Category: Poulos, T L.]]
		+	[[Category: Inhibitor binding]]
		+	[[Category: Nitric oxide synthase]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

OCA at 11:09, 14 December 2011

2011-12-14T11:09:06Z

←Older revision		Revision as of 11:09, 14 December 2011
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3ufq is ON HOLD	+	The entry 3ufq is ON HOLD until Paper Publication

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

	Description: Structure of rat nitric oxide synthase heme domain in complex with 6-(((3S,4S)-4-(((E)-5-(3-fluorophenyl)pent-4-en-1-yl)oxy)pyrrolidin-3-yl)methyl)-4-methylpyridin-2-amine		Description: Structure of rat nitric oxide synthase heme domain in complex with 6-(((3S,4S)-4-(((E)-5-(3-fluorophenyl)pent-4-en-1-yl)oxy)pyrrolidin-3-yl)methyl)-4-methylpyridin-2-amine

OCA: Protected "3ufq" [edit=sysop:move=sysop]

2011-11-09T11:18:19Z

Protected "3ufq" [edit=sysop:move=sysop]

←Older revision

Revision as of 11:18, 9 November 2011