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[[Image:1rs8.gif|left|200px]]


{{Structure
==Bovine endothelial NOS heme domain with D-lysine-D-nitroarginine amide bound==
|PDB= 1rs8 |SIZE=350|CAPTION= <scene name='initialview01'>1rs8</scene>, resolution 2.30&Aring;
<StructureSection load='1rs8' size='340' side='right'caption='[[1rs8]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=DP2:L-LYSYL-N~5~-[(Z)-(2,2-DIHYDROXYHYDRAZINO)(IMINO)METHYL]-L-ORNITHINAMIDE'>DP2</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>
<table><tr><td colspan='2'>[[1rs8]] 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=1RS8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RS8 FirstGlance]. <br>
|ACTIVITY= [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]  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
|GENE= endothelial nitric oxide synthase ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 Bos taurus])
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=DP2:L-LYSYL-N~5~-[(Z)-(2,2-DIHYDROXYHYDRAZINO)(IMINO)METHYL]-L-ORNITHINAMIDE'>DP2</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
}}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1rs8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rs8 OCA], [https://pdbe.org/1rs8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1rs8 RCSB], [https://www.ebi.ac.uk/pdbsum/1rs8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1rs8 ProSAT]</span></td></tr>
</table>
== 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.
== 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/rs/1rs8_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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/main_output.php?pdb_ID=1rs8 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
In a continuing effort to unravel the structural basis for isoform-selective inhibition of nitric oxide synthase (NOS) by various inhibitors, we have determined the crystal structures of the nNOS and eNOS heme domain bound with two D-nitroarginine-containing dipeptide inhibitors, D-Lys-D-Arg(NO)2-NH(2) and D-Phe-D-Arg(NO)2-NH(2). These two dipeptide inhibitors exhibit similar binding modes in the two constitutive NOS isozymes, which is consistent with the similar binding affinities for the two isoforms as determined by K(i) measurements. The D-nitroarginine-containing dipeptide inhibitors are not distinguished by the amino acid difference between nNOS and eNOS (Asp 597 and Asn 368, respectively) which is key in controlling isoform selection for nNOS over eNOS observed for the L-nitroarginine-containing dipeptide inhibitors reported previously [Flinspach, M., et al. (2004) Nat. Struct. Mol. Biol. 11, 54-59]. The lack of a free alpha-amino group on the D-nitroarginine moiety makes the dipeptide inhibitor steer away from the amino acid binding pocket near the active site. This allows the inhibitor to extend into the solvent-accessible channel farther away from the active site, which enables the inhibitors to explore new isoform-specific enzyme-inhibitor interactions. This might be the structural basis for why these D-nitroarginine-containing inhibitors are selective for nNOS (or eNOS) over iNOS.


'''Bovine endothelial NOS heme domain with D-lysine-D-nitroarginine amide bound'''
Structures of the neuronal and endothelial nitric oxide synthase heme domain with D-nitroarginine-containing dipeptide inhibitors bound.,Flinspach M, Li H, Jamal J, Yang W, Huang H, Silverman RB, Poulos TL Biochemistry. 2004 May 11;43(18):5181-7. PMID:15122883<ref>PMID:15122883</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1rs8" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
In a continuing effort to unravel the structural basis for isoform-selective inhibition of nitric oxide synthase (NOS) by various inhibitors, we have determined the crystal structures of the nNOS and eNOS heme domain bound with two D-nitroarginine-containing dipeptide inhibitors, D-Lys-D-Arg(NO)2-NH(2) and D-Phe-D-Arg(NO)2-NH(2). These two dipeptide inhibitors exhibit similar binding modes in the two constitutive NOS isozymes, which is consistent with the similar binding affinities for the two isoforms as determined by K(i) measurements. The D-nitroarginine-containing dipeptide inhibitors are not distinguished by the amino acid difference between nNOS and eNOS (Asp 597 and Asn 368, respectively) which is key in controlling isoform selection for nNOS over eNOS observed for the L-nitroarginine-containing dipeptide inhibitors reported previously [Flinspach, M., et al. (2004) Nat. Struct. Mol. Biol. 11, 54-59]. The lack of a free alpha-amino group on the D-nitroarginine moiety makes the dipeptide inhibitor steer away from the amino acid binding pocket near the active site. This allows the inhibitor to extend into the solvent-accessible channel farther away from the active site, which enables the inhibitors to explore new isoform-specific enzyme-inhibitor interactions. This might be the structural basis for why these D-nitroarginine-containing inhibitors are selective for nNOS (or eNOS) over iNOS.
*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]
 
== References ==
==About this Structure==
<references/>
1RS8 is a [[Single protein]] structure of 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=1RS8 OCA].
__TOC__
 
</StructureSection>
==Reference==
Structures of the neuronal and endothelial nitric oxide synthase heme domain with D-nitroarginine-containing dipeptide inhibitors bound., Flinspach M, Li H, Jamal J, Yang W, Huang H, Silverman RB, Poulos TL, Biochemistry. 2004 May 11;43(18):5181-7. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15122883 15122883]
[[Category: Bos taurus]]
[[Category: Bos taurus]]
[[Category: Nitric-oxide synthase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Flinspach M]]
[[Category: Flinspach, M.]]
[[Category: Huang H]]
[[Category: Huang, H.]]
[[Category: Jamal J]]
[[Category: Jamal, J.]]
[[Category: Li H]]
[[Category: Li, H.]]
[[Category: Poulos TL]]
[[Category: Poulos, T L.]]
[[Category: Silverman RB]]
[[Category: Silverman, R B.]]
[[Category: Yang W]]
[[Category: Yang, W.]]
[[Category: ACT]]
[[Category: CAC]]
[[Category: DP2]]
[[Category: GOL]]
[[Category: H4B]]
[[Category: HEM]]
[[Category: ZN]]
[[Category: heme-enzyme]]
[[Category: nitric oxide synthase]]
[[Category: oxidoreductase]]
 
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Retrieved from "https://proteopedia.org/1rs8"