4fvx - Revision history

OCA at 10:57, 13 August 2026

2026-08-13T10:57:59Z

← Older revision		Revision as of 10:57, 13 August 2026
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	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/NOS1_RAT NOS1_RAT] Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum.		[https://www.uniprot.org/uniprot/NOS1_RAT NOS1_RAT] Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum.
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Nitric oxide synthase (NOS) catalyzes the conversion of l-arginine to l-citrulline through the intermediate N(omega)-hydroxy-l-arginine (NHA), producing nitric oxide, an important mammalian signaling molecule. Several disease states are associated with improper regulation of nitric oxide production, making NOS a therapeutic target. The first step of the NOS reaction has been well-characterized and is presumed to proceed through a compound I heme species, analogous to the cytochrome P450 mechanism. The second step, however, is enzymatically unprecedented and is thought to occur via a ferric peroxo heme species. To gain insight into the details of this unique second step, we report here the synthesis of NHA analogues bearing guanidinium methyl or ethyl substitutions and their investigation as either inhibitors of or alternate substrates for NOS. Radiolabeling studies reveal that N(omega)-methoxy-l-arginine, an alternative NOS substrate, produces citrulline, nitric oxide, and methanol. On the basis of these results, we propose a mechanism for the second step of NOS catalysis in which a methylated nitric oxide species is released and is further metabolized by NOS. Crystal structures of our NHA analogues bound to nNOS have been determined, revealing the presence of an active site water molecule only in the presence of singly methylated analogues. Bulkier analogues displace this active site water molecule; a different mechanism is proposed in the absence of the water molecule. Our results provide new insights into the steric and stereochemical tolerance of the NOS active site and substrate capabilities of NOS.

			Methylated N(omega)-Hydroxy-l-arginine Analogues as Mechanistic Probes for the Second Step of the Nitric Oxide Synthase-Catalyzed Reaction.,Jansen Labby K, Li H, Roman LJ, Martasek P, Poulos TL, Silverman RB Biochemistry. 2013 May 7;52(18):3062-73. doi: 10.1021/bi301571v. Epub 2013 Apr, 26. PMID:23586781<ref>PMID:23586781</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 4fvx" 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>

OCA at 15:34, 14 March 2024

2024-03-14T15:34:53Z

← Older revision		Revision as of 15:34, 14 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4fvx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FVX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FVX FirstGlance]. <br>		<table><tr><td colspan='2'>[[4fvx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FVX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FVX FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2KJ:N~5~-(N-ETHOXYCARBAMIMIDOYL)-L-ORNITHINE'>2KJ</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=TFA:TRIFLUOROACETIC+ACID'>TFA</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]] 2Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2KJ:N~5~-(N-ETHOXYCARBAMIMIDOYL)-L-ORNITHINE'>2KJ</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=TFA:TRIFLUOROACETIC+ACID'>TFA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=4fvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fvx OCA], [https://pdbe.org/4fvx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fvx RCSB], [https://www.ebi.ac.uk/pdbsum/4fvx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fvx 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=4fvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fvx OCA], [https://pdbe.org/4fvx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fvx RCSB], [https://www.ebi.ac.uk/pdbsum/4fvx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fvx ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/NOS1_RAT NOS1_RAT] Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum.		[https://www.uniprot.org/uniprot/NOS1_RAT NOS1_RAT] Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum.
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Nitric oxide synthase (NOS) catalyzes the conversion of l-arginine to l-citrulline through the intermediate N(omega)-hydroxy-l-arginine (NHA), producing nitric oxide, an important mammalian signaling molecule. Several disease states are associated with improper regulation of nitric oxide production, making NOS a therapeutic target. The first step of the NOS reaction has been well-characterized and is presumed to proceed through a compound I heme species, analogous to the cytochrome P450 mechanism. The second step, however, is enzymatically unprecedented and is thought to occur via a ferric peroxo heme species. To gain insight into the details of this unique second step, we report here the synthesis of NHA analogues bearing guanidinium methyl or ethyl substitutions and their investigation as either inhibitors of or alternate substrates for NOS. Radiolabeling studies reveal that N(omega)-methoxy-l-arginine, an alternative NOS substrate, produces citrulline, nitric oxide, and methanol. On the basis of these results, we propose a mechanism for the second step of NOS catalysis in which a methylated nitric oxide species is released and is further metabolized by NOS. Crystal structures of our NHA analogues bound to nNOS have been determined, revealing the presence of an active site water molecule only in the presence of singly methylated analogues. Bulkier analogues displace this active site water molecule; a different mechanism is proposed in the absence of the water molecule. Our results provide new insights into the steric and stereochemical tolerance of the NOS active site and substrate capabilities of NOS.

	Methylated N(omega)-Hydroxy-l-arginine Analogues as Mechanistic Probes for the Second Step of the Nitric Oxide Synthase-Catalyzed Reaction.,Jansen Labby K, Li H, Roman LJ, Martasek P, Poulos TL, Silverman RB Biochemistry. 2013 May 7;52(18):3062-73. doi: 10.1021/bi301571v. Epub 2013 Apr, 26. PMID:23586781<ref>PMID:23586781</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4fvx" 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>

OCA at 20:12, 19 October 2022

2022-10-19T20:12:43Z

← Older revision		Revision as of 20:12, 19 October 2022
Line 1:		Line 1:

	==Structure of rat nNOS heme domain in complex with N(omega)-ethoxy-L-arginine==		==Structure of rat nNOS heme domain in complex with N(omega)-ethoxy-L-arginine==
	<StructureSection load='4fvx' size='340' side='right' caption='[[4fvx]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='4fvx' size='340' side='right'caption='[[4fvx]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4fvx]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Buffalo_rat Buffalo rat~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FVX OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4FVX FirstGlance]. <br>		<table><tr><td colspan='2'>[[4fvx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FVX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FVX FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2KJ:N~5~-(N-ETHOXYCARBAMIMIDOYL)-L-ORNITHINE'>2KJ</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=TFA:TRIFLUOROACETIC+ACID'>TFA</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=2KJ:N~5~-(N-ETHOXYCARBAMIMIDOYL)-L-ORNITHINE'>2KJ</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=TFA:TRIFLUOROACETIC+ACID'>TFA</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">[[4fvw\|4fvw]], [[4fvy\|4fvy]], [[4fvz\|4fvz]], [[4fw0\|4fw0]]</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=4fvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fvx OCA], [https://pdbe.org/4fvx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fvx RCSB], [https://www.ebi.ac.uk/pdbsum/4fvx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fvx ProSAT]</span></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Nos1, Bnos ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Nitric-oxide_synthase_(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=4fvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fvx OCA], [~~http~~://pdbe.org/4fvx PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4fvx RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4fvx PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4fvx ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[~~[http~~://www.uniprot.org/uniprot/NOS1_RAT NOS1_RAT]] Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum.		[https://www.uniprot.org/uniprot/NOS1_RAT NOS1_RAT] Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 4fvx" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4fvx" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Nitric Oxide Synthase 3D structures\|Nitric Oxide Synthase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Buffalo rat~~]]		[[Category: Large Structures]]
	[[Category: ~~Li, H~~]]		[[Category: Rattus norvegicus]]
	[[Category: ~~Poulos, T L~~]]		[[Category: Li H]]
	[[Category: ~~Nitric oxide synthase]]~~		[[Category: Poulos TL]]
	~~[[Category: Oxidoreductase]]~~
	~~[[Category: Substrate analog~~]]

OCA at 08:21, 15 November 2017

2017-11-15T08:21:49Z

← Older revision		Revision as of 08:21, 15 November 2017
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 4fvx" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4fvx" style="background-color:#fffaf0;"></div>

	~~==See Also==~~
	*[[Nitric Oxide Synthase\|Nitric Oxide Synthase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 11:23, 5 August 2016

2016-08-05T11:23:50Z

← Older revision		Revision as of 11:23, 5 August 2016
Line 1:		Line 1:

	==Structure of rat nNOS heme domain in complex with N(omega)-ethoxy-L-arginine==		==Structure of rat nNOS heme domain in complex with N(omega)-ethoxy-L-arginine==
	<StructureSection load='4fvx' size='340' side='right' caption='[[4fvx]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='4fvx' size='340' side='right' caption='[[4fvx]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4fvx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Rattus_norvegicus Rattus norvegicus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FVX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FVX FirstGlance]. <br>		<table><tr><td colspan='2'>[[4fvx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FVX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FVX FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2KJ:N~5~-(N-ETHOXYCARBAMIMIDOYL)-L-ORNITHINE'>2KJ</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=TFA:TRIFLUOROACETIC+ACID'>TFA</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=2KJ:N~5~-(N-ETHOXYCARBAMIMIDOYL)-L-ORNITHINE'>2KJ</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=TFA:TRIFLUOROACETIC+ACID'>TFA</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">[[4fvw\|4fvw]], [[4fvy\|4fvy]], [[4fvz\|4fvz]], [[4fw0\|4fw0]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4fvw\|4fvw]], [[4fvy\|4fvy]], [[4fvz\|4fvz]], [[4fw0\|4fw0]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Nos1, Bnos ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 ~~Rattus norvegicus~~])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Nos1, Bnos ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Nitric-oxide_synthase_(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=4fvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fvx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fvx RCSB], [http://www.ebi.ac.uk/pdbsum/4fvx 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=4fvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fvx OCA], [http://pdbe.org/4fvx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4fvx RCSB], [http://www.ebi.ac.uk/pdbsum/4fvx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4fvx 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 4fvx" style="background-color:#fffaf0;"></div>

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

OCA at 01:59, 25 December 2014

2014-12-25T01:59:39Z

← Older revision		Revision as of 01:59, 25 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=4fvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fvx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fvx RCSB], [http://www.ebi.ac.uk/pdbsum/4fvx 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=4fvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fvx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fvx RCSB], [http://www.ebi.ac.uk/pdbsum/4fvx PDBsum]</span></td></tr>
	</table>		</table>
			== Function ==
			[[http://www.uniprot.org/uniprot/NOS1_RAT NOS1_RAT]] Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 11:33, 21 December 2014

2014-12-21T11:33:18Z

← Older revision		Revision as of 11:33, 21 December 2014
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	~~{{STRUCTURE_4fvx\| PDB=4fvx \| SCENE= }}~~		==Structure of rat nNOS heme domain in complex with N(omega)-ethoxy-L-arginine==
	===Structure of rat nNOS heme domain in complex with N(omega)-ethoxy-L-arginine===		<StructureSection load='4fvx' size='340' side='right' caption='[[4fvx]], [[Resolution\|resolution]] 2.00Å' scene=''>
	~~{{ABSTRACT_PUBMED_23586781}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[4fvx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FVX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FVX FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2KJ:N~5~-(N-ETHOXYCARBAMIMIDOYL)-L-ORNITHINE'>2KJ</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=TFA:TRIFLUOROACETIC+ACID'>TFA</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">[[4fvw\|4fvw]], [[4fvy\|4fvy]], [[4fvz\|4fvz]], [[4fw0\|4fw0]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Nos1, Bnos ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])</td></tr>
			<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Nitric-oxide_synthase_(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=4fvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fvx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fvx RCSB], [http://www.ebi.ac.uk/pdbsum/4fvx PDBsum]</span></td></tr>
			</table>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Nitric oxide synthase (NOS) catalyzes the conversion of l-arginine to l-citrulline through the intermediate N(omega)-hydroxy-l-arginine (NHA), producing nitric oxide, an important mammalian signaling molecule. Several disease states are associated with improper regulation of nitric oxide production, making NOS a therapeutic target. The first step of the NOS reaction has been well-characterized and is presumed to proceed through a compound I heme species, analogous to the cytochrome P450 mechanism. The second step, however, is enzymatically unprecedented and is thought to occur via a ferric peroxo heme species. To gain insight into the details of this unique second step, we report here the synthesis of NHA analogues bearing guanidinium methyl or ethyl substitutions and their investigation as either inhibitors of or alternate substrates for NOS. Radiolabeling studies reveal that N(omega)-methoxy-l-arginine, an alternative NOS substrate, produces citrulline, nitric oxide, and methanol. On the basis of these results, we propose a mechanism for the second step of NOS catalysis in which a methylated nitric oxide species is released and is further metabolized by NOS. Crystal structures of our NHA analogues bound to nNOS have been determined, revealing the presence of an active site water molecule only in the presence of singly methylated analogues. Bulkier analogues displace this active site water molecule; a different mechanism is proposed in the absence of the water molecule. Our results provide new insights into the steric and stereochemical tolerance of the NOS active site and substrate capabilities of NOS.

	~~==Function==~~		Methylated N(omega)-Hydroxy-l-arginine Analogues as Mechanistic Probes for the Second Step of the Nitric Oxide Synthase-Catalyzed Reaction.,Jansen Labby K, Li H, Roman LJ, Martasek P, Poulos TL, Silverman RB Biochemistry. 2013 May 7;52(18):3062-73. doi: 10.1021/bi301571v. Epub 2013 Apr, 26. PMID:23586781<ref>PMID:23586781</ref>
	~~[[http://www.uniprot.org/uniprot/NOS1_RAT NOS1_RAT]] Produces nitric oxide~~ (NO) ~~which is a messenger molecule with diverse functions throughout~~ the ~~body~~. ~~In the brain and peripheral nervous system~~, ~~NO displays many properties of a neurotransmitter~~. ~~Inhibitory transmitter for non~~-~~adrenergic and non-cholinergic nerves in the colorectum~~. ~~Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR~~. ~~Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum~~.

	~~==About this Structure==~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[4fvx]] is~~ a ~~2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Rattus_norvegicus Rattus norvegicus]~~. ~~Full crystallographic information is available from [http:/~~/~~oca.weizmann.ac.il/oca-bin/ocashort?id=4FVX OCA].~~		</div>

	==~~Reference~~==		==See Also==
	~~<ref group~~=~~"xtra">PMID:023586781</ref>~~<references ~~group="xtra"~~/><~~references~~/>		*[[Nitric Oxide Synthase\|Nitric Oxide Synthase]]
			== References ==
			<references/>
			__TOC__
			</StructureSection>
	[[Category: Rattus norvegicus]]		[[Category: Rattus norvegicus]]
	[[Category: Li, H.]]		[[Category: Li, H]]
	[[Category: Poulos, T L.]]		[[Category: Poulos, T L]]
	[[Category: Nitric oxide synthase]]		[[Category: Nitric oxide synthase]]
	[[Category: Oxidoreductase]]		[[Category: Oxidoreductase]]
	[[Category: Substrate analog]]		[[Category: Substrate analog]]

OCA at 14:17, 10 July 2013

2013-07-10T14:17:26Z

← Older revision		Revision as of 14:17, 10 July 2013
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	==About this Structure==		==About this Structure==
	[[4fvx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FVX OCA].		[[4fvx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FVX OCA].

			==Reference==
			<ref group="xtra">PMID:023586781</ref><references group="xtra"/><references/>
	[[Category: Rattus norvegicus]]		[[Category: Rattus norvegicus]]
	[[Category: Li, H.]]		[[Category: Li, H.]]

OCA at 07:19, 16 May 2013

2013-05-16T07:19:50Z

← Older revision		Revision as of 07:19, 16 May 2013
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	~~'''Unreleased structure'''~~		{{STRUCTURE_4fvx\| PDB=4fvx \| SCENE= }}
			===Structure of rat nNOS heme domain in complex with N(omega)-ethoxy-L-arginine===
			{{ABSTRACT_PUBMED_23586781}}

	~~The entry 4fvx~~ is ~~ON HOLD until Paper Publication~~		==Function==
			[[http://www.uniprot.org/uniprot/NOS1_RAT NOS1_RAT]] Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum.

	~~Authors~~: Li, H., Poulos, T.L.		==About this Structure==
			[[4fvx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FVX OCA].
	~~Description~~: ~~Structure of rat nNOS heme domain in complex with N(omega)-ethoxy-L-arginine~~		[[Category: Rattus norvegicus]]
			[[Category: Li, H.]]
			[[Category: Poulos, T L.]]
			[[Category: Nitric oxide synthase]]
			[[Category: Oxidoreductase]]
			[[Category: Substrate analog]]

OCA at 04:55, 8 August 2012

2012-08-08T04:55:14Z

← Older revision		Revision as of 04:55, 8 August 2012
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 4fvx is ON HOLD		The entry 4fvx is ON HOLD until Paper Publication

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

	Description: Structure of rat nNOS heme domain in complex with N(omega)-ethoxy-L-arginine		Description: Structure of rat nNOS heme domain in complex with N(omega)-ethoxy-L-arginine