View source for 2orp

==Murine inducible nitric oxide synthase oxygenase domain (delta 114) 2-[4-(2-Imidazol-1-yl-6-methyl-pyrimidin-4-yl)-1-isobutyryl-piperazin-2-yl]-N-[2-(4-methoxy-phenyl)-ethyl]-acetamide complex==
<StructureSection load='2orp' size='340' side='right' caption='[[2orp]], [[Resolution|resolution]] 1.97&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2orp]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ORP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ORP FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=R86:2-{(2R)-4-[2-(1H-IMIDAZOL-1-YL)-6-METHYLPYRIMIDIN-4-YL]-1-ISOBUTYRYLPIPERAZIN-2-YL}-N-[2-(4-METHOXYPHENYL)ETHYL]ACETAMIDE'>R86</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1dd7|1dd7]], [[2oro|2oro]], [[1nos|1nos]], [[1noc|1noc]], [[2nos|2nos]], [[1nod|1nod]], [[1nsi|1nsi]], [[2orq|2orq]], [[2orr|2orr]], [[2ors|2ors]], [[2ort|2ort]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Nos2, Inosl ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Nitric-oxide_synthase_(NADPH_dependent) Nitric-oxide synthase (NADPH dependent)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.39 1.14.13.39] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2orp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2orp OCA], [http://pdbe.org/2orp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2orp RCSB], [http://www.ebi.ac.uk/pdbsum/2orp PDBsum]</span></td></tr>
</table>
== Function ==
[[http://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/or/2orp_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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/chain_selection.php?pdb_ID=2ata ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
By the screening of a combinatorial library for inhibitors of nitric oxide (NO) formation by the inducible isoform of nitric oxide synthase (iNOS) using a whole-cell assay, 2-(imidazol-1-yl)pyrimidines were identified. Compounds were found to inhibit the dimerization of iNOS monomers, thus preventing the formation of the dimeric, active form of the enzyme. Optimization led to the selection of the potent, selective, and orally available iNOS dimerization inhibitor, 21b, which significantly ameliorated adjuvant-induced arthritis in a rat model. Analysis of the crystal structure of the 21b--iNOS monomer complex provided a rationalization for both the SAR and the mechanism by which 21b blocks the formation of the protein--protein interaction present in the dimeric form of iNOS.

Design, synthesis, and activity of 2-imidazol-1-ylpyrimidine derived inducible nitric oxide synthase dimerization inhibitors.,Davey DD, Adler M, Arnaiz D, Eagen K, Erickson S, Guilford W, Kenrick M, Morrissey MM, Ohlmeyer M, Pan G, Paradkar VM, Parkinson J, Polokoff M, Saionz K, Santos C, Subramanyam B, Vergona R, Wei RG, Whitlow M, Ye B, Zhao ZS, Devlin JJ, Phillips G J Med Chem. 2007 Mar 22;50(6):1146-57. Epub 2007 Feb 23. PMID:17315988<ref>PMID:17315988</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 2orp" style="background-color:#fffaf0;"></div>

==See Also==
*[[Nitric Oxide Synthase|Nitric Oxide Synthase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Lk3 transgenic mice]]
[[Category: Adler, M]]
[[Category: Whitlow, M]]
[[Category: Dimerization]]
[[Category: Heme]]
[[Category: Inhibitor]]
[[Category: L-arginine monooxygenase]]
[[Category: Nitric oxide]]
[[Category: No]]
[[Category: Oxidoreductase]]