6cif - Revision history

OCA at 15:05, 4 October 2023

OCA — Wed, 04 Oct 2023 15:05:27 GMT

←Older revision		Revision as of 15:05, 4 October 2023
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	<StructureSection load='6cif' size='340' side='right'caption='[[6cif]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='6cif' size='340' side='right'caption='[[6cif]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6cif]] is a 4 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=6CIF OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6CIF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6cif]] is a 4 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=6CIF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CIF FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=F2J:N-[1-(piperidin-4-yl)-1H-indol-5-yl]thiophene-2-carboximidamide'>F2J</scene>, <scene name='pdbligand=GD:GADOLINIUM+ATOM'>GD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=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]] 2.2Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NOS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=F2J:N-[1-(piperidin-4-yl)-1H-indol-5-yl]thiophene-2-carboximidamide'>F2J</scene>, <scene name='pdbligand=GD:GADOLINIUM+ATOM'>GD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=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=6cif FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cif OCA], [https://pdbe.org/6cif PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cif RCSB], [https://www.ebi.ac.uk/pdbsum/6cif PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cif 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=6cif FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cif OCA], [~~http~~://pdbe.org/6cif PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6cif RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6cif PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6cif ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/NOS3_HUMAN NOS3_HUMAN]] Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets.<ref>PMID:17264164</ref> Isoform eNOS13C: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1.<ref>PMID:17264164</ref>	+	[https://www.uniprot.org/uniprot/NOS3_HUMAN NOS3_HUMAN] Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets.<ref>PMID:17264164</ref> Isoform eNOS13C: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1.<ref>PMID:17264164</ref>
	<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: Chreifi, G]]	+	[[Category: Chreifi G]]
-	[[Category: Li, H]]	+	[[Category: Li H]]
-	[[Category: Poulos~~, T L]]~~	+	[[Category: Poulos TL]]
-	~~[[Category: Nitric oxide synthase inhibitor complex heme enzyme]]~~	+
-	~~[[Category: Oxidoreductase~~]]	+

OCA at 10:45, 1 January 2020

OCA — Wed, 01 Jan 2020 10:45:50 GMT

←Older revision		Revision as of 10:45, 1 January 2020
Line 1:		Line 1:

	==Structure of the human endothelial nitric oxide synthase heme domain in complex with N-(1-(Piperidin-4-yl)indolin-5-yl)thiophene-2-carboximidamide==		==Structure of the human endothelial nitric oxide synthase heme domain in complex with N-(1-(Piperidin-4-yl)indolin-5-yl)thiophene-2-carboximidamide==
-	<StructureSection load='6cif' size='340' side='right' caption='[[6cif]], [[Resolution\|resolution]] 2.20Å' scene=''>	+	<StructureSection load='6cif' size='340' side='right'caption='[[6cif]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6cif]] is a 4 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=6CIF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CIF FirstGlance]. <br>		<table><tr><td colspan='2'>[[6cif]] is a 4 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=6CIF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CIF FirstGlance]. <br>
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 6cif" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6cif" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Nitric Oxide Synthase 3D structures\|Nitric Oxide Synthase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 25:		Line 28:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Chreifi, G]]		[[Category: Chreifi, G]]
	[[Category: Li, H]]		[[Category: Li, H]]

OCA at 12:41, 7 November 2018

OCA — Wed, 07 Nov 2018 12:41:10 GMT

←Older revision		Revision as of 12:41, 7 November 2018
Line 3:		Line 3:
	<StructureSection load='6cif' size='340' side='right' caption='[[6cif]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='6cif' size='340' side='right' caption='[[6cif]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6cif]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CIF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CIF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6cif]] is a 4 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=6CIF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CIF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=F2J:N-[1-(piperidin-4-yl)-1H-indol-5-yl]thiophene-2-carboximidamide'>F2J</scene>, <scene name='pdbligand=GD:GADOLINIUM+ATOM'>GD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=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=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=F2J:N-[1-(piperidin-4-yl)-1H-indol-5-yl]thiophene-2-carboximidamide'>F2J</scene>, <scene name='pdbligand=GD:GADOLINIUM+ATOM'>GD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NOS3 ([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=6cif FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cif OCA], [http://pdbe.org/6cif PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cif RCSB], [http://www.ebi.ac.uk/pdbsum/6cif PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cif 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=6cif FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cif OCA], [http://pdbe.org/6cif PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cif RCSB], [http://www.ebi.ac.uk/pdbsum/6cif PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cif ProSAT]</span></td></tr>
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Chreifi, G]]		[[Category: Chreifi, G]]
	[[Category: Li, H]]		[[Category: Li, H]]

OCA at 06:49, 31 October 2018

OCA — Wed, 31 Oct 2018 06:49:11 GMT

←Older revision		Revision as of 06:49, 31 October 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6cif is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Structure of the human endothelial nitric oxide synthase heme domain in complex with N-(1-(Piperidin-4-yl)indolin-5-yl)thiophene-2-carboximidamide==
		+	<StructureSection load='6cif' size='340' side='right' caption='[[6cif]], [[Resolution\|resolution]] 2.20Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6cif]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CIF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CIF FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=F2J:N-[1-(piperidin-4-yl)-1H-indol-5-yl]thiophene-2-carboximidamide'>F2J</scene>, <scene name='pdbligand=GD:GADOLINIUM+ATOM'>GD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=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=6cif FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cif OCA], [http://pdbe.org/6cif PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cif RCSB], [http://www.ebi.ac.uk/pdbsum/6cif PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cif ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/NOS3_HUMAN NOS3_HUMAN]] Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets.<ref>PMID:17264164</ref> Isoform eNOS13C: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1.<ref>PMID:17264164</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The overproduction of nitric oxide in the brain by neuronal nitric oxide synthase (nNOS) is associated with a number of neurodegenerative diseases. Although inhibiting nNOS is an important therapeutic goal, it is important not to inhibit endothelial NOS (eNOS) because of the critical role played by eNOS in maintaining vascular tone. While it has been possible to develop nNOS selective aminopyridine inhibitors, many of the most potent and selective inhibitors exhibit poor bioavailability properties. Our group and others have turned to more biocompatible thiophene-2-carboximidamide (T2C) inhibitors as potential nNOS selective inhibitors. We have used crystallography and computational methods to better understand how and why two commercially developed T2C inhibitors exhibit selectivity for human nNOS over human eNOS. As with many of the aminopyridine inhibitors, a critical active site Asp residue in nNOS versus Asn in eNOS is largely responsible for controlling selectivity. We also present thermodynamic integration results to better understand the change in p Ka and thus the charge of inhibitors once bound to the active site. In addition, relative free energy calculations underscore the importance of enhanced electrostatic stabilization of inhibitors bound to the nNOS active site compared to eNOS.

-	~~Authors: Chreifi, G~~., Li, H., ~~Poulos~~, T.L.	+	Structural Basis for Isoform Selective Nitric Oxide Synthase Inhibition by Thiophene-2-carboximidamides.,Li H, Evenson RJ, Chreifi G, Silverman RB, Poulos TL Biochemistry. 2018 Oct 24. doi: 10.1021/acs.biochem.8b00895. PMID:30335983<ref>PMID:30335983</ref>

-	~~Description: Structure~~ of the ~~human endothelial nitric oxide synthase heme domain in complex with N~~-(1-~~(Piperidin-4-yl)indolin-5-yl)thiophene-2-carboximidamide~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	~~[[Category: Li, H]]~~	+	<div class="pdbe-citations 6cif" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Chreifi, G]]		[[Category: Chreifi, G]]
-	[[Category: Poulos, T.L]]	+	[[Category: Li, H]]
		+	[[Category: Poulos, T L]]
		+	[[Category: Nitric oxide synthase inhibitor complex heme enzyme]]
		+	[[Category: Oxidoreductase]]

OCA at 06:06, 21 March 2018

OCA — Wed, 21 Mar 2018 06:06:32 GMT

←Older revision		Revision as of 06:06, 21 March 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

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

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

OCA — Thu, 08 Mar 2018 03:46:03 GMT

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

←Older revision

Revision as of 03:46, 8 March 2018

OCA: New page: '''Unreleased structure''' The entry 6cif is ON HOLD Authors: Chreifi, G., Li, H., Poulos, T.L. Description: Structure of the human endothelial nitric oxide synthase heme domain in com...

OCA — Thu, 08 Mar 2018 03:46:02 GMT

New page: '''Unreleased structure''' The entry 6cif is ON HOLD Authors: Chreifi, G., Li, H., Poulos, T.L. Description: Structure of the human endothelial nitric oxide synthase heme domain in com...

New page

'''Unreleased structure'''

The entry 6cif is ON HOLD

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

Description: Structure of the human endothelial nitric oxide synthase heme domain in complex with N-(1-(Piperidin-4-yl)indolin-5-yl)thiophene-2-carboximidamide
[[Category: Unreleased Structures]]
[[Category: Li, H]]
[[Category: Chreifi, G]]
[[Category: Poulos, T.L]]