1m8e - Revision history

OCA at 07:41, 14 February 2024

2024-02-14T07:41:18Z

←Older revision		Revision as of 07:41, 14 February 2024
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	<StructureSection load='1m8e' size='340' side='right'caption='[[1m8e]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='1m8e' size='340' side='right'caption='[[1m8e]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1m8e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Lk3_transgenic_mice Lk3 transgenic mice~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M8E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M8E FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1m8e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M8E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M8E FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=7NI:7~~-~~NITROINDAZOLE'>7NI</scene>~~, ~~<scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</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;~~'>~~[[1nod\|1nod]], [[1m8d\|1m8d]], [[1m8h\|1m8h]], [[1m8i\|1m8i]], [[1m9j\|1m9j]], [[1m9k\|1m9k]], [[1m9m\|1m9m]], [[1m9q\|1m9q]], [[1m9r\|1m9r]], [[1m9t\|1m9t]], [[3nod\|3nod]]~~</~~div~~><~~/td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7NI:7-NITROINDAZOLE'>7NI</scene>, <scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></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=1m8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m8e OCA], [https://pdbe.org/1m8e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m8e RCSB], [https://www.ebi.ac.uk/pdbsum/1m8e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m8e 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=1m8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m8e OCA], [https://pdbe.org/1m8e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m8e RCSB], [https://www.ebi.ac.uk/pdbsum/1m8e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m8e ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/NOS2_MOUSE NOS2_MOUSE]] Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such COX2.<ref>PMID:16373578</ref>	+	[https://www.uniprot.org/uniprot/NOS2_MOUSE NOS2_MOUSE] Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such COX2.<ref>PMID:16373578</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1m8e ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1m8e ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Nitric oxide is a key signaling molecule in many biological processes, making regulation of nitric oxide levels highly desirable for human medicine and for advancing our understanding of basic physiology. Designing inhibitors to specifically target one of the three nitric oxide synthase (NOS) isozymes that form nitric oxide from the L-Arg substrate poses a significant challenge due to the overwhelmingly conserved active sites. We report here 10 new X-ray crystallographic structures of inducible and endothelial NOS oxygenase domains cocrystallized with chlorzoxazone and four nitroindazoles: 5-nitroindazole, 6-nitroindazole, 7-nitroindazole, and 3-bromo-7-nitroindazole. Each of these bicyclic aromatic inhibitors has only one hydrogen bond donor and therefore cannot form the bidentate hydrogen bonds that the L-Arg substrate makes with Glu371. Instead, all of these inhibitors induce a conformational change in Glu371, creating an active site with altered molecular recognition properties. The cost of this conformational change is approximately 1-2 kcal, based on our measured constants for inhibitor binding to the wild-type and E371A mutant proteins. These inhibitors derive affinity by pi-stacking above the heme and replacing both intramolecular (Glu371-Met368) and intermolecular (substrate-Trp366) hydrogen bonds to the beta-sheet architecture underlying the active site. When bound to NOS, high-affinity inhibitors in this class are planar, whereas weaker inhibitors are nonplanar. Isozyme differences were observed in the pterin cofactor site, the heme propionate, and inhibitor positions. Computational docking predictions match the crystallographic results, including the Glu371 conformational change and inhibitor-binding orientations, and support a combined crystallographic and computational approach to isozyme-specific NOS inhibitor analysis and design.
-
-	Conformational changes in nitric oxide synthases induced by chlorzoxazone and nitroindazoles: crystallographic and computational analyses of inhibitor potency.,Rosenfeld RJ, Garcin ED, Panda K, Andersson G, Aberg A, Wallace AV, Morris GM, Olson AJ, Stuehr DJ, Tainer JA, Getzoff ED Biochemistry. 2002 Nov 26;41(47):13915-25. PMID:12437348<ref>PMID:12437348</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 1m8e" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Lk3 transgenic mice~~]]	+	[[Category: Mus musculus]]
-	[[Category: Aberg, A]]	+	[[Category: Aberg A]]
-	[[Category: Andersson, G]]	+	[[Category: Andersson G]]
-	[[Category: Garcin~~, E D~~]]	+	[[Category: Garcin ED]]
-	[[Category: Getzoff~~, E D~~]]	+	[[Category: Getzoff ED]]
-	[[Category: Panda, K]]	+	[[Category: Panda K]]
-	[[Category: Rosenfeld~~, R J~~]]	+	[[Category: Rosenfeld RJ]]
-	[[Category: Stuehr~~, D J~~]]	+	[[Category: Stuehr DJ]]
-	[[Category: Tainer~~, J A~~]]	+	[[Category: Tainer JA]]
-	[[Category: Wallace~~, A V]]~~	+	[[Category: Wallace AV]]
-	~~[[Category: Oxidoreductase~~]]	+

OCA at 05:58, 28 April 2021

2021-04-28T05:58:43Z

←Older revision		Revision as of 05:58, 28 April 2021
Line 3:		Line 3:
	<StructureSection load='1m8e' size='340' side='right'caption='[[1m8e]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='1m8e' size='340' side='right'caption='[[1m8e]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1m8e]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M8E OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1M8E FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1m8e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M8E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M8E FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7NI:7-NITROINDAZOLE'>7NI</scene>, <scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7NI:7-NITROINDAZOLE'>7NI</scene>, <scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1nod\|1nod]], [[1m8d\|1m8d]], [[1m8h\|1m8h]], [[1m8i\|1m8i]], [[1m9j\|1m9j]], [[1m9k\|1m9k]], [[1m9m\|1m9m]], [[1m9q\|1m9q]], [[1m9r\|1m9r]], [[1m9t\|1m9t]], [[3nod\|3nod]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1nod\|1nod]], [[1m8d\|1m8d]], [[1m8h\|1m8h]], [[1m8i\|1m8i]], [[1m9j\|1m9j]], [[1m9k\|1m9k]], [[1m9m\|1m9m]], [[1m9q\|1m9q]], [[1m9r\|1m9r]], [[1m9t\|1m9t]], [[3nod\|3nod]]</div></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=1m8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m8e OCA], [~~http~~://pdbe.org/1m8e PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1m8e RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1m8e PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1m8e 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=1m8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m8e OCA], [https://pdbe.org/1m8e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m8e RCSB], [https://www.ebi.ac.uk/pdbsum/1m8e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m8e ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/NOS2_MOUSE NOS2_MOUSE]] Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such COX2.<ref>PMID:16373578</ref>	+	[[https://www.uniprot.org/uniprot/NOS2_MOUSE NOS2_MOUSE]] Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such COX2.<ref>PMID:16373578</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 32:		Line 32:

	==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 09:28, 24 July 2019

2019-07-24T09:28:52Z

←Older revision		Revision as of 09:28, 24 July 2019
Line 1:		Line 1:

	==inducible nitric oxide synthase with 7-nitroindazole bound==		==inducible nitric oxide synthase with 7-nitroindazole bound==
-	<StructureSection load='1m8e' size='340' side='right' caption='[[1m8e]], [[Resolution\|resolution]] 2.90Å' scene=''>	+	<StructureSection load='1m8e' size='340' side='right'caption='[[1m8e]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1m8e]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M8E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1M8E FirstGlance]. <br>		<table><tr><td colspan='2'>[[1m8e]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M8E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1M8E FirstGlance]. <br>
Line 15:		Line 15:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/m8/1m8e_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/m8/1m8e_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 30:		Line 30:
	</div>		</div>
	<div class="pdbe-citations 1m8e" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1m8e" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Nitric Oxide Synthase\|Nitric Oxide Synthase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Lk3 transgenic mice]]		[[Category: Lk3 transgenic mice]]
	[[Category: Aberg, A]]		[[Category: Aberg, A]]

OCA at 10:42, 18 October 2017

2017-10-18T10:42:32Z

←Older revision		Revision as of 10:42, 18 October 2017
Line 1:		Line 1:
		+
	==inducible nitric oxide synthase with 7-nitroindazole bound==		==inducible nitric oxide synthase with 7-nitroindazole bound==
	<StructureSection load='1m8e' size='340' side='right' caption='[[1m8e]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='1m8e' size='340' side='right' caption='[[1m8e]], [[Resolution\|resolution]] 2.90Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1nod\|1nod]], [[1m8d\|1m8d]], [[1m8h\|1m8h]], [[1m8i\|1m8i]], [[1m9j\|1m9j]], [[1m9k\|1m9k]], [[1m9m\|1m9m]], [[1m9q\|1m9q]], [[1m9r\|1m9r]], [[1m9t\|1m9t]], [[3nod\|3nod]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1nod\|1nod]], [[1m8d\|1m8d]], [[1m8h\|1m8h]], [[1m8i\|1m8i]], [[1m9j\|1m9j]], [[1m9k\|1m9k]], [[1m9m\|1m9m]], [[1m9q\|1m9q]], [[1m9r\|1m9r]], [[1m9t\|1m9t]], [[3nod\|3nod]]</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=1m8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m8e OCA], [http://pdbe.org/1m8e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1m8e RCSB], [http://www.ebi.ac.uk/pdbsum/1m8e 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=1m8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m8e OCA], [http://pdbe.org/1m8e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1m8e RCSB], [http://www.ebi.ac.uk/pdbsum/1m8e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1m8e ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1m8e ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 29:		Line 30:
	</div>		</div>
	<div class="pdbe-citations 1m8e" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1m8e" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Nitric Oxide Synthase\|Nitric Oxide Synthase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 23:19, 11 September 2015

2015-09-11T23:19:58Z

←Older revision		Revision as of 23:19, 11 September 2015
Line 2:		Line 2:
	<StructureSection load='1m8e' size='340' side='right' caption='[[1m8e]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='1m8e' size='340' side='right' caption='[[1m8e]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1m8e]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Mus_musculus Mus musculus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M8E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1M8E FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1m8e]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M8E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1M8E FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7NI:7-NITROINDAZOLE'>7NI</scene>, <scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7NI:7-NITROINDAZOLE'>7NI</scene>, <scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1nod\|1nod]], [[1m8d\|1m8d]], [[1m8h\|1m8h]], [[1m8i\|1m8i]], [[1m9j\|1m9j]], [[1m9k\|1m9k]], [[1m9m\|1m9m]], [[1m9q\|1m9q]], [[1m9r\|1m9r]], [[1m9t\|1m9t]], [[3nod\|3nod]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1nod\|1nod]], [[1m8d\|1m8d]], [[1m8h\|1m8h]], [[1m8i\|1m8i]], [[1m9j\|1m9j]], [[1m9k\|1m9k]], [[1m9m\|1m9m]], [[1m9q\|1m9q]], [[1m9r\|1m9r]], [[1m9t\|1m9t]], [[3nod\|3nod]]</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=1m8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m8e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1m8e RCSB], [http://www.ebi.ac.uk/pdbsum/1m8e 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=1m8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m8e OCA], [http://pdbe.org/1m8e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1m8e RCSB], [http://www.ebi.ac.uk/pdbsum/1m8e PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 28:		Line 28:
	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 1m8e" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 35:		Line 36:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Mus musculus]]~~	+	[[Category: Lk3 transgenic mice]]
-	~~[[Category: Nitric-oxide synthase~~]]	+
	[[Category: Aberg, A]]		[[Category: Aberg, A]]
	[[Category: Andersson, G]]		[[Category: Andersson, G]]

OCA at 20:46, 25 December 2014

2014-12-25T20:46:26Z

←Older revision		Revision as of 20:46, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1m8e]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M8E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1M8E FirstGlance]. <br>		<table><tr><td colspan='2'>[[1m8e]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M8E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1M8E FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7NI:7-NITROINDAZOLE'>7NI</scene>, <scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7NI:7-NITROINDAZOLE'>7NI</scene>, <scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1nod\|1nod]], [[1m8d\|1m8d]], [[1m8h\|1m8h]], [[1m8i\|1m8i]], [[1m9j\|1m9j]], [[1m9k\|1m9k]], [[1m9m\|1m9m]], [[1m9q\|1m9q]], [[1m9r\|1m9r]], [[1m9t\|1m9t]], [[3nod\|3nod]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1nod\|1nod]], [[1m8d\|1m8d]], [[1m8h\|1m8h]], [[1m8i\|1m8i]], [[1m9j\|1m9j]], [[1m9k\|1m9k]], [[1m9m\|1m9m]], [[1m9q\|1m9q]], [[1m9r\|1m9r]], [[1m9t\|1m9t]], [[3nod\|3nod]]</td></tr>
-	<tr><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 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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1m8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m8e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1m8e RCSB], [http://www.ebi.ac.uk/pdbsum/1m8e 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=1m8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m8e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1m8e RCSB], [http://www.ebi.ac.uk/pdbsum/1m8e PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/NOS2_MOUSE NOS2_MOUSE]] Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such COX2.<ref>PMID:16373578</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 35:		Line 37:
	[[Category: Mus musculus]]		[[Category: Mus musculus]]
	[[Category: Nitric-oxide synthase]]		[[Category: Nitric-oxide synthase]]
-	[[Category: Aberg, A.]]	+	[[Category: Aberg, A]]
-	[[Category: Andersson, G.]]	+	[[Category: Andersson, G]]
-	[[Category: Garcin, E D.]]	+	[[Category: Garcin, E D]]
-	[[Category: Getzoff, E D.]]	+	[[Category: Getzoff, E D]]
-	[[Category: Panda, K.]]	+	[[Category: Panda, K]]
-	[[Category: Rosenfeld, R J.]]	+	[[Category: Rosenfeld, R J]]
-	[[Category: Stuehr, D J.]]	+	[[Category: Stuehr, D J]]
-	[[Category: Tainer, J A.]]	+	[[Category: Tainer, J A]]
-	[[Category: Wallace, A V.]]	+	[[Category: Wallace, A V]]
	[[Category: Oxidoreductase]]		[[Category: Oxidoreductase]]

OCA at 15:12, 28 September 2014

2014-09-28T15:12:04Z

←Older revision		Revision as of 15:12, 28 September 2014
Line 1:		Line 1:
-	[[~~Image:~~1m8e.~~png~~\|~~left~~\|200px]]	+	==inducible nitric oxide synthase with 7-nitroindazole bound==
		+	<StructureSection load='1m8e' size='340' side='right' caption='[[1m8e]], [[Resolution\|resolution]] 2.90Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1m8e]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M8E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1M8E FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7NI:7-NITROINDAZOLE'>7NI</scene>, <scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1nod\|1nod]], [[1m8d\|1m8d]], [[1m8h\|1m8h]], [[1m8i\|1m8i]], [[1m9j\|1m9j]], [[1m9k\|1m9k]], [[1m9m\|1m9m]], [[1m9q\|1m9q]], [[1m9r\|1m9r]], [[1m9t\|1m9t]], [[3nod\|3nod]]</td></tr>
		+	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1m8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m8e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1m8e RCSB], [http://www.ebi.ac.uk/pdbsum/1m8e PDBsum]</span></td></tr>
		+	<table>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/m8/1m8e_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Nitric oxide is a key signaling molecule in many biological processes, making regulation of nitric oxide levels highly desirable for human medicine and for advancing our understanding of basic physiology. Designing inhibitors to specifically target one of the three nitric oxide synthase (NOS) isozymes that form nitric oxide from the L-Arg substrate poses a significant challenge due to the overwhelmingly conserved active sites. We report here 10 new X-ray crystallographic structures of inducible and endothelial NOS oxygenase domains cocrystallized with chlorzoxazone and four nitroindazoles: 5-nitroindazole, 6-nitroindazole, 7-nitroindazole, and 3-bromo-7-nitroindazole. Each of these bicyclic aromatic inhibitors has only one hydrogen bond donor and therefore cannot form the bidentate hydrogen bonds that the L-Arg substrate makes with Glu371. Instead, all of these inhibitors induce a conformational change in Glu371, creating an active site with altered molecular recognition properties. The cost of this conformational change is approximately 1-2 kcal, based on our measured constants for inhibitor binding to the wild-type and E371A mutant proteins. These inhibitors derive affinity by pi-stacking above the heme and replacing both intramolecular (Glu371-Met368) and intermolecular (substrate-Trp366) hydrogen bonds to the beta-sheet architecture underlying the active site. When bound to NOS, high-affinity inhibitors in this class are planar, whereas weaker inhibitors are nonplanar. Isozyme differences were observed in the pterin cofactor site, the heme propionate, and inhibitor positions. Computational docking predictions match the crystallographic results, including the Glu371 conformational change and inhibitor-binding orientations, and support a combined crystallographic and computational approach to isozyme-specific NOS inhibitor analysis and design.

-	~~{{STRUCTURE_1m8e\| PDB=1m8e \| SCENE= }}~~	+	Conformational changes in nitric oxide synthases induced by chlorzoxazone and nitroindazoles: crystallographic and computational analyses of inhibitor potency.,Rosenfeld RJ, Garcin ED, Panda K, Andersson G, Aberg A, Wallace AV, Morris GM, Olson AJ, Stuehr DJ, Tainer JA, Getzoff ED Biochemistry. 2002 Nov 26;41(47):13915-25. PMID:12437348<ref>PMID:12437348</ref>

-	~~===inducible nitric oxide synthase with 7-nitroindazole bound===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_12437348}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[1m8e]] is~~ a ~~2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Mus_musculus Mus musculus]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=1M8E OCA].~~	+

	==See Also==		==See Also==
	*[[Nitric Oxide Synthase\|Nitric Oxide Synthase]]		*[[Nitric Oxide Synthase\|Nitric Oxide Synthase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:012437348<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Mus musculus]]		[[Category: Mus musculus]]
	[[Category: Nitric-oxide synthase]]		[[Category: Nitric-oxide synthase]]

OCA at 21:26, 20 October 2012

2012-10-20T21:26:04Z

←Older revision		Revision as of 21:26, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[1m8e]] is a 2 chain structure ~~of [[Nitric Oxide Synthase]]~~ with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M8E OCA].	+	[[1m8e]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M8E OCA].

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

OCA: Protected "1m8e" [edit=sysop:move=sysop]

2012-07-27T13:14:30Z

Protected "1m8e" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:14, 27 July 2012

OCA at 13:14, 27 July 2012

2012-07-27T13:14:29Z

←Older revision		Revision as of 13:14, 27 July 2012
Line 1:		Line 1:
-	{{Seed}}
	[[Image:1m8e.png\|left\|200px]]		[[Image:1m8e.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_1m8e", 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_1m8e\| PDB=1m8e \| SCENE= }}		{{STRUCTURE_1m8e\| PDB=1m8e \| SCENE= }}

	===inducible nitric oxide synthase with 7-nitroindazole bound===		===inducible nitric oxide synthase with 7-nitroindazole bound===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_12437348}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 12437348 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_12437348}}		{{ABSTRACT_PUBMED_12437348}}

	==About this Structure==		==About this Structure==
-	~~1M8E~~ is a 2 ~~chains~~ structure of ~~sequences~~ from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M8E OCA].	+	[[1m8e]] is a 2 chain structure of [[Nitric Oxide Synthase]] with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M8E OCA].
		+
		+	==See Also==
		+	*[[Nitric Oxide Synthase\|Nitric Oxide Synthase]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~12437348~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:012437348</ref><references group="xtra"/>
	[[Category: Mus musculus]]		[[Category: Mus musculus]]
	[[Category: Nitric-oxide synthase]]		[[Category: Nitric-oxide synthase]]
Line 36:		Line 27:
	[[Category: Wallace, A V.]]		[[Category: Wallace, A V.]]
	[[Category: Oxidoreductase]]		[[Category: Oxidoreductase]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 18 06:43:05 2009''