3n5q - Revision history

OCA at 09:58, 14 February 2024

OCA — Wed, 14 Feb 2024 09:58:52 GMT

←Older revision		Revision as of 09:58, 14 February 2024
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	<StructureSection load='3n5q' size='340' side='right'caption='[[3n5q]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='3n5q' size='340' side='right'caption='[[3n5q]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3n5q]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Bovin Bovin~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N5Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3N5Q FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3n5q]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N5Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3N5Q FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAD:CACODYLIC+ACID'>CAD</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=XFN:6,6-[(5-AMINOBENZENE-1,3-DIYL)DIETHANE-2,1-DIYL]BIS(4-METHYLPYRIDIN-2-AMINE)'>XFN</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]] 2.9Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3n5p\|3n5p]], [[3n5r\|3n5r]], [[3n5s\|3n5s]], [[3n5t\|3n5t]], [[3n5v\|3n5v]], [[3n5w\|3n5w]], [[3n5x\|3n5x]], [[3n5y\|3n5y]], [[3n5z\|3n5z]], [[3n60\|3n60]], [[3n61\|3n61]], [[3n62\|3n62]], [[3n63\|3n63]], [[3n64\|3n64]], [[3n65\|3n65]], [[3n66\|3n66]], [[3n67\|3n67]], [[3n68\|3n68]], [[3n69\|3n69]], [[3n6a\|3n6a]], [[3n6b\|3n6b]], [[3n6c\|3n6c]], [[3n6d\|3n6d]], [[3n6e\|3n6e]], [[3n6f\|3n6f]], [[3n6g\|3n6g]]</div></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAD:CACODYLIC+ACID'>CAD</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=XFN:6,6-[(5-AMINOBENZENE-1,3-DIYL)DIETHANE-2,1-DIYL]BIS(4-METHYLPYRIDIN-2-AMINE)'>XFN</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 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</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=3n5q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n5q OCA], [https://pdbe.org/3n5q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3n5q RCSB], [https://www.ebi.ac.uk/pdbsum/3n5q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3n5q 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=3n5q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n5q OCA], [https://pdbe.org/3n5q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3n5q RCSB], [https://www.ebi.ac.uk/pdbsum/3n5q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3n5q ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/NOS3_BOVIN NOS3_BOVIN]] 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.	+	[https://www.uniprot.org/uniprot/NOS3_BOVIN NOS3_BOVIN] 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.
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	In previous studies [Delker, S. L., et al. (2010), J. Am. Chem. Soc. 132, 5437-5442], we determined the crystal structures of neuronal nitric oxide synthase (nNOS) in complex with nNOS-selective chiral pyrrolidine inhibitors, designed to have an aminopyridine group bound over the heme where it can electrostatically interact with the conserved active site Glu residue. However, in addition to the expected binding mode with the (S,S)-cis inhibitors, an unexpected "flipped" orientation was observed for the (R,R)-cis enantiomers. In the flipped mode, the aminopyridine extends out of the active site where it interacts with one heme propionate. This prompted us to design and synthesize symmetric "double-headed" inhibitors with an aminopyridine at each end of a bridging ring structure [Xue, F., Delker, S. L., Li, H., Fang, J., Jamal, J., Martasek, P., Roman, L. J., Poulos, T. L., and Silverman, R. B. Symmetric double-headed aminopyridines, a novel strategy for potent and membrane-permeable inhibitors of neuronal nitric oxide synthase. J. Med. Chem. (submitted for publication)]. One aminopyridine should interact with the active site Glu and the other with the heme propionate. Crystal structures of these double-headed aminopyridine inhibitors in complexes with nNOS show unexpected and significant protein and heme conformational changes induced by inhibitor binding that result in removal of the tetrahydrobiopterin (H(4)B) cofactor and creation of a new Zn(2+) site. These changes are due to binding of a second inhibitor molecule that results in the displacement of H(4)B and the placement of the inhibitor pyridine group in position to serve as a Zn(2+) ligand together with Asp, His, and a chloride ion. Binding of the second inhibitor molecule and generation of the Zn(2+) site do not occur in eNOS. Structural requirements for creation of the new Zn(2+) site in nNOS were analyzed in detail. These observations open the way for the potential design of novel inhibitors selective for nNOS.	+
-		+
-	Role of zinc in isoform-selective inhibitor binding to neuronal nitric oxide synthase .,Delker SL, Xue F, Li H, Jamal J, Silverman RB, Poulos TL Biochemistry. 2010 Dec 28;49(51):10803-10. Epub 2010 Dec 7. PMID:21138269<ref>PMID:21138269</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3n5q" 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: ~~Bovin~~]]	+	[[Category: Bos taurus]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Delker~~, S L~~]]	+	[[Category: Delker SL]]
-	[[Category: Li, H]]	+	[[Category: Li H]]
-	[[Category: Poulos~~, T L]]~~	+	[[Category: Poulos TL]]
-	~~[[Category: Heme enzyme]]~~	+
-	~~[[Category: Nitric oxide synthase]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]~~	+
-	~~[[Category: Substrate inhibitor~~]]	+

OCA at 06:55, 12 May 2022

OCA — Thu, 12 May 2022 06:55:36 GMT

←Older revision		Revision as of 06:55, 12 May 2022
Line 3:		Line 3:
	<StructureSection load='3n5q' size='340' side='right'caption='[[3n5q]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='3n5q' size='340' side='right'caption='[[3n5q]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3n5q]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N5Q OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3N5Q FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3n5q]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N5Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3N5Q FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAD:CACODYLIC+ACID'>CAD</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=XFN:6,6-[(5-AMINOBENZENE-1,3-DIYL)DIETHANE-2,1-DIYL]BIS(4-METHYLPYRIDIN-2-AMINE)'>XFN</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=CAD:CACODYLIC+ACID'>CAD</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=XFN:6,6-[(5-AMINOBENZENE-1,3-DIYL)DIETHANE-2,1-DIYL]BIS(4-METHYLPYRIDIN-2-AMINE)'>XFN</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">[[3n5p\|3n5p]], [[3n5r\|3n5r]], [[3n5s\|3n5s]], [[3n5t\|3n5t]], [[3n5v\|3n5v]], [[3n5w\|3n5w]], [[3n5x\|3n5x]], [[3n5y\|3n5y]], [[3n5z\|3n5z]], [[3n60\|3n60]], [[3n61\|3n61]], [[3n62\|3n62]], [[3n63\|3n63]], [[3n64\|3n64]], [[3n65\|3n65]], [[3n66\|3n66]], [[3n67\|3n67]], [[3n68\|3n68]], [[3n69\|3n69]], [[3n6a\|3n6a]], [[3n6b\|3n6b]], [[3n6c\|3n6c]], [[3n6d\|3n6d]], [[3n6e\|3n6e]], [[3n6f\|3n6f]], [[3n6g\|3n6g]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3n5p\|3n5p]], [[3n5r\|3n5r]], [[3n5s\|3n5s]], [[3n5t\|3n5t]], [[3n5v\|3n5v]], [[3n5w\|3n5w]], [[3n5x\|3n5x]], [[3n5y\|3n5y]], [[3n5z\|3n5z]], [[3n60\|3n60]], [[3n61\|3n61]], [[3n62\|3n62]], [[3n63\|3n63]], [[3n64\|3n64]], [[3n65\|3n65]], [[3n66\|3n66]], [[3n67\|3n67]], [[3n68\|3n68]], [[3n69\|3n69]], [[3n6a\|3n6a]], [[3n6b\|3n6b]], [[3n6c\|3n6c]], [[3n6d\|3n6d]], [[3n6e\|3n6e]], [[3n6f\|3n6f]], [[3n6g\|3n6g]]</div></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=9913 BOVIN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NOS3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</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=3n5q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n5q OCA], [~~http~~://pdbe.org/3n5q PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3n5q RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3n5q PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3n5q 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=3n5q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n5q OCA], [https://pdbe.org/3n5q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3n5q RCSB], [https://www.ebi.ac.uk/pdbsum/3n5q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3n5q ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/NOS3_BOVIN NOS3_BOVIN]] 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.	+	[[https://www.uniprot.org/uniprot/NOS3_BOVIN NOS3_BOVIN]] 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.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 23:

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

OCA at 11:23, 17 July 2019

OCA — Wed, 17 Jul 2019 11:23:50 GMT

←Older revision		Revision as of 11:23, 17 July 2019
Line 1:		Line 1:

	==Structure of endothelial nitric oxide synthase heme domain complexed with 6,6'-(2,2'-(5-amino-1,3-phenylene)bis(ethane-2,1-diyl))bis(4-methylpyridin-2-amine)==		==Structure of endothelial nitric oxide synthase heme domain complexed with 6,6'-(2,2'-(5-amino-1,3-phenylene)bis(ethane-2,1-diyl))bis(4-methylpyridin-2-amine)==
-	<StructureSection load='3n5q' size='340' side='right' caption='[[3n5q]], [[Resolution\|resolution]] 2.90Å' scene=''>	+	<StructureSection load='3n5q' size='340' side='right'caption='[[3n5q]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3n5q]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N5Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3N5Q FirstGlance]. <br>		<table><tr><td colspan='2'>[[3n5q]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N5Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3N5Q FirstGlance]. <br>
Line 29:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Bovin]]		[[Category: Bovin]]
		+	[[Category: Large Structures]]
	[[Category: Delker, S L]]		[[Category: Delker, S L]]
	[[Category: Li, H]]		[[Category: Li, H]]

OCA at 17:31, 4 August 2016

OCA — Thu, 04 Aug 2016 17:31:53 GMT

←Older revision		Revision as of 17:31, 4 August 2016
Line 1:		Line 1:
		+
	==Structure of endothelial nitric oxide synthase heme domain complexed with 6,6'-(2,2'-(5-amino-1,3-phenylene)bis(ethane-2,1-diyl))bis(4-methylpyridin-2-amine)==		==Structure of endothelial nitric oxide synthase heme domain complexed with 6,6'-(2,2'-(5-amino-1,3-phenylene)bis(ethane-2,1-diyl))bis(4-methylpyridin-2-amine)==
	<StructureSection load='3n5q' size='340' side='right' caption='[[3n5q]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='3n5q' size='340' side='right' caption='[[3n5q]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3n5q]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Bos_taurus Bos taurus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N5Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3N5Q FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3n5q]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N5Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3N5Q FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAD:CACODYLIC+ACID'>CAD</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=XFN:6,6-[(5-AMINOBENZENE-1,3-DIYL)DIETHANE-2,1-DIYL]BIS(4-METHYLPYRIDIN-2-AMINE)'>XFN</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=CAD:CACODYLIC+ACID'>CAD</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=XFN:6,6-[(5-AMINOBENZENE-1,3-DIYL)DIETHANE-2,1-DIYL]BIS(4-METHYLPYRIDIN-2-AMINE)'>XFN</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">[[3n5p\|3n5p]], [[3n5r\|3n5r]], [[3n5s\|3n5s]], [[3n5t\|3n5t]], [[3n5v\|3n5v]], [[3n5w\|3n5w]], [[3n5x\|3n5x]], [[3n5y\|3n5y]], [[3n5z\|3n5z]], [[3n60\|3n60]], [[3n61\|3n61]], [[3n62\|3n62]], [[3n63\|3n63]], [[3n64\|3n64]], [[3n65\|3n65]], [[3n66\|3n66]], [[3n67\|3n67]], [[3n68\|3n68]], [[3n69\|3n69]], [[3n6a\|3n6a]], [[3n6b\|3n6b]], [[3n6c\|3n6c]], [[3n6d\|3n6d]], [[3n6e\|3n6e]], [[3n6f\|3n6f]], [[3n6g\|3n6g]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3n5p\|3n5p]], [[3n5r\|3n5r]], [[3n5s\|3n5s]], [[3n5t\|3n5t]], [[3n5v\|3n5v]], [[3n5w\|3n5w]], [[3n5x\|3n5x]], [[3n5y\|3n5y]], [[3n5z\|3n5z]], [[3n60\|3n60]], [[3n61\|3n61]], [[3n62\|3n62]], [[3n63\|3n63]], [[3n64\|3n64]], [[3n65\|3n65]], [[3n66\|3n66]], [[3n67\|3n67]], [[3n68\|3n68]], [[3n69\|3n69]], [[3n6a\|3n6a]], [[3n6b\|3n6b]], [[3n6c\|3n6c]], [[3n6d\|3n6d]], [[3n6e\|3n6e]], [[3n6f\|3n6f]], [[3n6g\|3n6g]]</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=9913 ~~Bos taurus~~])</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=9913 BOVIN])</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=3n5q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n5q OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3n5q RCSB], [http://www.ebi.ac.uk/pdbsum/3n5q 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=3n5q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n5q OCA], [http://pdbe.org/3n5q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3n5q RCSB], [http://www.ebi.ac.uk/pdbsum/3n5q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3n5q ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	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 3n5q" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 26:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Bos taurus]]~~	+	[[Category: Bovin]]
-	~~[[Category: Nitric-oxide synthase~~]]	+
	[[Category: Delker, S L]]		[[Category: Delker, S L]]
	[[Category: Li, H]]		[[Category: Li, H]]

OCA at 17:38, 24 December 2014

OCA — Wed, 24 Dec 2014 17:38:04 GMT

←Older revision		Revision as of 17:38, 24 December 2014
Line 9:		Line 9:
	<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=3n5q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n5q OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3n5q RCSB], [http://www.ebi.ac.uk/pdbsum/3n5q 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=3n5q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n5q OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3n5q RCSB], [http://www.ebi.ac.uk/pdbsum/3n5q PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/NOS3_BOVIN NOS3_BOVIN]] 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.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 09:33, 9 December 2014

OCA — Tue, 09 Dec 2014 09:33:32 GMT

←Older revision		Revision as of 09:33, 9 December 2014
Line 1:		Line 1:
-	[[~~Image:~~3n5q.~~png~~\|~~left~~\|~~200px~~]]	+	==Structure of endothelial nitric oxide synthase heme domain complexed with 6,6'-(2,2'-(5-amino-1,3-phenylene)bis(ethane-2,1-diyl))bis(4-methylpyridin-2-amine)==
		+	<StructureSection load='3n5q' size='340' side='right' caption='[[3n5q]], [[Resolution\|resolution]] 2.90Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3n5q]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N5Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3N5Q FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAD:CACODYLIC+ACID'>CAD</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=XFN:6,6-[(5-AMINOBENZENE-1,3-DIYL)DIETHANE-2,1-DIYL]BIS(4-METHYLPYRIDIN-2-AMINE)'>XFN</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">[[3n5p\|3n5p]], [[3n5r\|3n5r]], [[3n5s\|3n5s]], [[3n5t\|3n5t]], [[3n5v\|3n5v]], [[3n5w\|3n5w]], [[3n5x\|3n5x]], [[3n5y\|3n5y]], [[3n5z\|3n5z]], [[3n60\|3n60]], [[3n61\|3n61]], [[3n62\|3n62]], [[3n63\|3n63]], [[3n64\|3n64]], [[3n65\|3n65]], [[3n66\|3n66]], [[3n67\|3n67]], [[3n68\|3n68]], [[3n69\|3n69]], [[3n6a\|3n6a]], [[3n6b\|3n6b]], [[3n6c\|3n6c]], [[3n6d\|3n6d]], [[3n6e\|3n6e]], [[3n6f\|3n6f]], [[3n6g\|3n6g]]</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=9913 Bos taurus])</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=3n5q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n5q OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3n5q RCSB], [http://www.ebi.ac.uk/pdbsum/3n5q PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	In previous studies [Delker, S. L., et al. (2010), J. Am. Chem. Soc. 132, 5437-5442], we determined the crystal structures of neuronal nitric oxide synthase (nNOS) in complex with nNOS-selective chiral pyrrolidine inhibitors, designed to have an aminopyridine group bound over the heme where it can electrostatically interact with the conserved active site Glu residue. However, in addition to the expected binding mode with the (S,S)-cis inhibitors, an unexpected "flipped" orientation was observed for the (R,R)-cis enantiomers. In the flipped mode, the aminopyridine extends out of the active site where it interacts with one heme propionate. This prompted us to design and synthesize symmetric "double-headed" inhibitors with an aminopyridine at each end of a bridging ring structure [Xue, F., Delker, S. L., Li, H., Fang, J., Jamal, J., Martasek, P., Roman, L. J., Poulos, T. L., and Silverman, R. B. Symmetric double-headed aminopyridines, a novel strategy for potent and membrane-permeable inhibitors of neuronal nitric oxide synthase. J. Med. Chem. (submitted for publication)]. One aminopyridine should interact with the active site Glu and the other with the heme propionate. Crystal structures of these double-headed aminopyridine inhibitors in complexes with nNOS show unexpected and significant protein and heme conformational changes induced by inhibitor binding that result in removal of the tetrahydrobiopterin (H(4)B) cofactor and creation of a new Zn(2+) site. These changes are due to binding of a second inhibitor molecule that results in the displacement of H(4)B and the placement of the inhibitor pyridine group in position to serve as a Zn(2+) ligand together with Asp, His, and a chloride ion. Binding of the second inhibitor molecule and generation of the Zn(2+) site do not occur in eNOS. Structural requirements for creation of the new Zn(2+) site in nNOS were analyzed in detail. These observations open the way for the potential design of novel inhibitors selective for nNOS.

-	~~{{STRUCTURE_3n5q\| PDB=3n5q \| SCENE= }}~~	+	Role of zinc in isoform-selective inhibitor binding to neuronal nitric oxide synthase .,Delker SL, Xue F, Li H, Jamal J, Silverman RB, Poulos TL Biochemistry. 2010 Dec 28;49(51):10803-10. Epub 2010 Dec 7. PMID:21138269<ref>PMID:21138269</ref>

-	~~===Structure of endothelial nitric oxide synthase heme domain complexed with 6~~,~~6'-(2,2'-(5-amino-1,3-phenylene)bis(ethane-2,1-diyl))bis(4-methylpyridin-2-amine)===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_21138269}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[3n5q]] is~~ a ~~2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Bos_taurus Bos taurus]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=3N5Q OCA].~~	+

	==See Also==		==See Also==
	*[[Nitric Oxide Synthase\|Nitric Oxide Synthase]]		*[[Nitric Oxide Synthase\|Nitric Oxide Synthase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:021138269<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Bos taurus]]		[[Category: Bos taurus]]
	[[Category: Nitric-oxide synthase]]		[[Category: Nitric-oxide synthase]]
-	[[Category: Delker, S L.]]	+	[[Category: Delker, S L]]
-	[[Category: Li, H.]]	+	[[Category: Li, H]]
-	[[Category: Poulos, T L.]]	+	[[Category: Poulos, T L]]
	[[Category: Heme enzyme]]		[[Category: Heme enzyme]]
	[[Category: Nitric oxide synthase]]		[[Category: Nitric oxide synthase]]

OCA at 07:36, 20 October 2012

OCA — Sat, 20 Oct 2012 07:36:05 GMT

←Older revision		Revision as of 07:36, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[3n5q]] is a 2 chain structure ~~of [[Nitric Oxide Synthase]]~~ with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N5Q OCA].	+	[[3n5q]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N5Q OCA].

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

OCA at 16:50, 25 July 2012

OCA — Wed, 25 Jul 2012 16:50:48 GMT

←Older revision		Revision as of 16:50, 25 July 2012
Line 1:		Line 1:
-	[[Image:3n5q.~~jpg~~\|left\|200px]]	+	[[Image:3n5q.png\|left\|200px]]

-	<!--
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-	-->
	{{STRUCTURE_3n5q\| PDB=3n5q \| SCENE= }}		{{STRUCTURE_3n5q\| PDB=3n5q \| SCENE= }}

	===Structure of endothelial nitric oxide synthase heme domain complexed with 6,6'-(2,2'-(5-amino-1,3-phenylene)bis(ethane-2,1-diyl))bis(4-methylpyridin-2-amine)===		===Structure of endothelial nitric oxide synthase heme domain complexed with 6,6'-(2,2'-(5-amino-1,3-phenylene)bis(ethane-2,1-diyl))bis(4-methylpyridin-2-amine)===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_21138269}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 21138269 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_21138269}}		{{ABSTRACT_PUBMED_21138269}}

	==About this Structure==		==About this Structure==
-	[[3n5q]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N5Q OCA].	+	[[3n5q]] is a 2 chain structure of [[Nitric Oxide Synthase]] with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N5Q OCA].
		+
		+	==See Also==
		+	*[[Nitric Oxide Synthase\|Nitric Oxide Synthase]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~21138269~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:021138269</ref><references group="xtra"/>
	[[Category: Bos taurus]]		[[Category: Bos taurus]]
	[[Category: Nitric-oxide synthase]]		[[Category: Nitric-oxide synthase]]
Line 28:		Line 20:
	[[Category: Li, H.]]		[[Category: Li, H.]]
	[[Category: Poulos, T L.]]		[[Category: Poulos, T L.]]
		+	[[Category: Heme enzyme]]
		+	[[Category: Nitric oxide synthase]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
		+	[[Category: Substrate inhibitor]]

OCA: Protected "3n5q" [edit=sysop:move=sysop]

OCA — Wed, 09 Feb 2011 06:08:47 GMT

Protected "3n5q" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:08, 9 February 2011

OCA at 06:08, 9 February 2011

OCA — Wed, 09 Feb 2011 06:08:45 GMT

←Older revision		Revision as of 06:08, 9 February 2011
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3n5q.jpg\|left\|200px]]

-	The ~~entry 3n5q~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3n5q", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3n5q\| PDB=3n5q \| SCENE= }}

-	~~Authors: Delker~~, ~~S.L.~~, Li, H., ~~Poulos, T.L.~~	+	===Structure of endothelial nitric oxide synthase heme domain complexed with 6,6'-(2,2'-(5-amino-1,3-phenylene)bis(ethane-2,1-diyl))bis(4-methylpyridin-2-amine)===

-	Description: Structure of endothelial nitric oxide synthase heme domain complexed with 6,6'-(2,2'-(5-amino-1,3-phenylene)bis(ethane-2,1-diyl))bis(4-methylpyridin-2-amine)

-	~~''Page seeded by~~ [http://oca.weizmann.ac.il/oca OCA ] ~~on Wed Jun 16 08~~:29:~~01 2010''~~	+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_21138269}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 21138269 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_21138269}}
		+
		+	==About this Structure==
		+	[[3n5q]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N5Q OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:21138269</ref><references group="xtra"/>
		+	[[Category: Bos taurus]]
		+	[[Category: Nitric-oxide synthase]]
		+	[[Category: Delker, S L.]]
		+	[[Category: Li, H.]]
		+	[[Category: Poulos, T L.]]