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1rs9

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[[Image:1rs9.gif|left|200px]]
 
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==Bovine endothelial NOS heme domain with D-phenylalanine-D-nitroarginine amide bound==
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The line below this paragraph, containing "STRUCTURE_1rs9", creates the "Structure Box" on the page.
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<StructureSection load='1rs9' size='340' side='right'caption='[[1rs9]], [[Resolution|resolution]] 2.22&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1rs9]] 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=1RS9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RS9 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.22&#8491;</td></tr>
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<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=D7P:D-PHENYLALANYL-N~5~-[(2,2-DIHYDROXYHYDRAZINO)(IMINO)METHYL]-D-ORNITHINAMIDE'>D7P</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>
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{{STRUCTURE_1rs9| PDB=1rs9 | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1rs9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rs9 OCA], [https://pdbe.org/1rs9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1rs9 RCSB], [https://www.ebi.ac.uk/pdbsum/1rs9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1rs9 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rs/1rs9_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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=1rs9 ConSurf].
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<div style="clear:both"></div>
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'''Bovine endothelial NOS heme domain with D-phenylalanine-D-nitroarginine amide bound'''
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==See Also==
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*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]
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__TOC__
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==Overview==
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</StructureSection>
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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.
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==About this Structure==
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1RS9 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=1RS9 OCA].
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==Reference==
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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]
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[[Category: Bos taurus]]
[[Category: Bos taurus]]
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[[Category: Nitric-oxide synthase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Flinspach M]]
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[[Category: Flinspach, M.]]
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[[Category: Huang H]]
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[[Category: Huang, H.]]
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[[Category: Jamal J]]
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[[Category: Jamal, J.]]
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[[Category: Li H]]
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[[Category: Li, H.]]
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[[Category: Poulos TL]]
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[[Category: Poulos, T L.]]
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[[Category: Silverman RB]]
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[[Category: Silverman, R B.]]
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[[Category: Yang W]]
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[[Category: Yang, W.]]
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[[Category: Heme-enzyme]]
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[[Category: Nitric oxide synthase]]
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[[Category: Oxidoreductase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 07:51:07 2008''
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Current revision

Bovine endothelial NOS heme domain with D-phenylalanine-D-nitroarginine amide bound

PDB ID 1rs9

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