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1nsi

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[[Image:1nsi.gif|left|200px]]<br /><applet load="1nsi" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1nsi, resolution 2.55&Aring;" />
 
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'''HUMAN INDUCIBLE NITRIC OXIDE SYNTHASE, ZN-BOUND, L-ARG COMPLEX'''<br />
 
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==Overview==
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==HUMAN INDUCIBLE NITRIC OXIDE SYNTHASE, ZN-BOUND, L-ARG COMPLEX==
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The crystal structures of the heme domain of human inducible nitric-oxide synthase (NOS-2) in zinc-free and -bound states have been solved. In the zinc-free structure, two symmetry-related cysteine residues form a disulfide bond. In the zinc-bound state, these same two cysteine residues form part of a zinc-tetrathiolate (ZnS(4)) center indistinguishable from that observed in the endothelial isoform (NOS-3). As in NOS-3, ZnS(4) plays a key role in stabilizing intersubunit contacts and in maintaining the integrity of the cofactor (tetrahydrobiopterin) binding site of NOS-2. A comparison of NOS-2 and NOS-3 structures illustrates the conservation of quaternary structure, tertiary topology, and substrate and cofactor binding sites, in addition to providing insights on isoform-specific inhibitor design. The structural comparison also reveals that pterin binding does not preferentially stabilize the dimer interface of NOS-2 over NOS-3.
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<StructureSection load='1nsi' size='340' side='right'caption='[[1nsi]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1nsi]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NSI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NSI 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]] 2.55&#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=ARG:ARGININE'>ARG</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=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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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=1nsi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nsi OCA], [https://pdbe.org/1nsi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nsi RCSB], [https://www.ebi.ac.uk/pdbsum/1nsi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nsi ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/NOS2_HUMAN NOS2_HUMAN] 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.
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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/ns/1nsi_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=1nsi ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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Known diseases associated with this structure: Hypertension, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=163730 163730]], Malaria, resistance to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=163730 163730]]
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*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]
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__TOC__
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==About this Structure==
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</StructureSection>
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1NSI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=HEM:'>HEM</scene>, <scene name='pdbligand=H4B:'>H4B</scene>, <scene name='pdbligand=ARG:'>ARG</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NSI OCA].
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==Reference==
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Crystal structures of zinc-free and -bound heme domain of human inducible nitric-oxide synthase. Implications for dimer stability and comparison with endothelial nitric-oxide synthase., Li H, Raman CS, Glaser CB, Blasko E, Young TA, Parkinson JF, Whitlow M, Poulos TL, J Biol Chem. 1999 Jul 23;274(30):21276-84. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10409685 10409685]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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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: Blasko E]]
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[[Category: Blasko, E.]]
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[[Category: Glaser CB]]
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[[Category: Glaser, C B.]]
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[[Category: Li H]]
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[[Category: Li, H.]]
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[[Category: Parkinson JF]]
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[[Category: Parkinson, J F.]]
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[[Category: Poulos TL]]
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[[Category: Poulos, T L.]]
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[[Category: Raman CS]]
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[[Category: Raman, C S.]]
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[[Category: Whitlow M]]
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[[Category: Whitlow, M.]]
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[[Category: Young TA]]
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[[Category: Young, T A.]]
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[[Category: ARG]]
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[[Category: GOL]]
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[[Category: H4B]]
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[[Category: HEM]]
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[[Category: SO4]]
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[[Category: ZN]]
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[[Category: heme protein]]
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[[Category: nitric oxide synthase]]
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[[Category: tetrahydrobiopterin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:09:31 2008''
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Current revision

HUMAN INDUCIBLE NITRIC OXIDE SYNTHASE, ZN-BOUND, L-ARG COMPLEX

PDB ID 1nsi

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