View source for 1vaf


==Inducible nitric oxide synthase oxygenase domain complexed with the inhibitor AR-R17477==
<StructureSection load='1vaf' size='340' side='right'caption='[[1vaf]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1vaf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VAF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1VAF 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]] 2.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ARR:N-(4-{2-[(3-CHLOROBENZYL)AMINO]ETHYL}PHENYL)THIOPHENE-2-CARBOXIMIDAMIDE'>ARR</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=1vaf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vaf OCA], [https://pdbe.org/1vaf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1vaf RCSB], [https://www.ebi.ac.uk/pdbsum/1vaf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1vaf ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NOS2_MOUSE NOS2_MOUSE] 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.<ref>PMID:16373578</ref> 
== 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/va/1vaf_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=1vaf ConSurf].
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== Publication Abstract from PubMed ==
The high level of amino acid conservation and structural similarity of the substrate-binding sites of the oxygenase domains of the nitric oxide synthase (NOS) isoforms (eNOSoxy, iNOSoxy, nNOSoxy) make the interpretation of the structural basis of inhibitor isoform specificity a challenge, and provide few clues for the design of new selective compounds. Crystal structures of iNOSoxy and nNOSoxy complexed with the neuronal NOS-specific inhibitor AR-R17447 suggest that specificity is provided by the interaction of the chlorophenyl group with an isoform-unique substrate access channel residue (L337 in rat neuronal NOS, N115 in mouse inducible NOS). This is confirmed by biochemical analysis of site-directed mutants. Inhibitors combining guanidinium-like structural motifs with long chains specifically targeting this residue are good candidates for rational isoform-specific drug design. Based on this finding, modifications of AR-R17447 to improve the specificity for the human isoforms are suggested.

Structures of nitric oxide synthase isoforms complexed with the inhibitor AR-R17477 suggest a rational basis for specificity and inhibitor design.,Fedorov R, Vasan R, Ghosh DK, Schlichting I Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):5892-7. Epub 2004 Apr 7. PMID:15071192<ref>PMID:15071192</ref>

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

==See Also==
*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Fedorov R]]
[[Category: Ghosh DK]]
[[Category: Schlichting I]]
[[Category: Vasan R]]