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[[Image:2nsi.gif|left|200px]]
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{{STRUCTURE_2nsi|  PDB=2nsi  |  SCENE=  }}
'''HUMAN INDUCIBLE NITRIC OXIDE SYNTHASE, ZN-FREE, SEITU COMPLEX'''


==HUMAN INDUCIBLE NITRIC OXIDE SYNTHASE, ZN-FREE, SEITU COMPLEX==
<StructureSection load='2nsi' size='340' side='right'caption='[[2nsi]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2nsi]] 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=2NSI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NSI FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=ITU:ETHYLISOTHIOUREA'>ITU</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2nsi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nsi OCA], [https://pdbe.org/2nsi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nsi RCSB], [https://www.ebi.ac.uk/pdbsum/2nsi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nsi ProSAT]</span></td></tr>
</table>
== Function ==
[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.
== 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/ns/2nsi_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=2nsi ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


==Overview==
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:10409685<ref>PMID:10409685</ref>
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.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2NSI is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NSI OCA].
</div>
<div class="pdbe-citations 2nsi" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
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://www.ncbi.nlm.nih.gov/pubmed/10409685 10409685]
*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Nitric-oxide synthase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Blasko E]]
[[Category: Blasko, E.]]
[[Category: Glaser CB]]
[[Category: Glaser, C B.]]
[[Category: Li H]]
[[Category: Li, H.]]
[[Category: Parkinson JF]]
[[Category: Parkinson, J F.]]
[[Category: Poulos TL]]
[[Category: Poulos, T L.]]
[[Category: Raman CS]]
[[Category: Raman, C S.]]
[[Category: Whitlow M]]
[[Category: Whitlow, M.]]
[[Category: Young TA]]
[[Category: Young, T A.]]
[[Category: Heme protein]]
[[Category: Nitric oxide synthase]]
[[Category: Tetrahydrobiopterin]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 09:51:34 2008''

Latest revision as of 08:21, 30 October 2024

HUMAN INDUCIBLE NITRIC OXIDE SYNTHASE, ZN-FREE, SEITU COMPLEX

2nsi, resolution 3.00Å

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