2ort

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[[Image:2ort.gif|left|200px]]
 
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{{Structure
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==Murine Inducible Nitric Oxide Synthase Oxygenase Domain (Delta 114) 1-Benzo[1,3]dioxol-5-ylmethyl-3S-(4-imidazol-1-yl-phenoxy)-piperidine Complex==
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|PDB= 2ort |SIZE=350|CAPTION= <scene name='initialview01'>2ort</scene>, resolution 1.87&Aring;
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<StructureSection load='2ort' size='340' side='right'caption='[[2ort]], [[Resolution|resolution]] 1.87&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=342:(3S)-1-(1,3-BENZODIOXOL-5-YLMETHYL)-3-[4-(1H-IMIDAZOL-1-YL)PHENOXY]PIPERIDINE'>342</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>
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<table><tr><td colspan='2'>[[2ort]] is a 1 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=2ORT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ORT FirstGlance]. <br>
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|ACTIVITY= <span class='plainlinks'>[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] </span>
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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]] 1.87&#8491;</td></tr>
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|GENE= Nos2, Inosl ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=342:(3S)-1-(1,3-BENZODIOXOL-5-YLMETHYL)-3-[4-(1H-IMIDAZOL-1-YL)PHENOXY]PIPERIDINE'>342</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
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|DOMAIN=
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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=2ort FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ort OCA], [https://pdbe.org/2ort PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ort RCSB], [https://www.ebi.ac.uk/pdbsum/2ort PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ort ProSAT]</span></td></tr>
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|RELATEDENTRY=[[1dd7|1DD7]], [[2oro|2ORO]], [[2orp|2ORP]], [[2orq|2ORQ]], [[2orr|2ORR]], [[2ors|2ORS]], [[1nos|1NOS]], [[1noc|1NOC]], [[2nos|2NOS]], [[1nod|1NOD]], [[1nsi|1NSI]]
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ort FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ort OCA], [http://www.ebi.ac.uk/pdbsum/2ort PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2ort RCSB]</span>
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== Function ==
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}}
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[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>
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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/or/2ort_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=2ort ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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'''Murine Inducible Nitric Oxide Synthase Oxygenase Domain (Delta 114) 1-Benzo[1,3]dioxol-5-ylmethyl-3S-(4-imidazol-1-yl-phenoxy)-piperidine Complex'''
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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>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2ort" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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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.
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*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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2ORT is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ORT OCA].
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__TOC__
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</StructureSection>
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==Reference==
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[[Category: Large Structures]]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/17315988 17315988]
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[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Nitric-oxide synthase]]
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[[Category: Adler M]]
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[[Category: Single protein]]
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[[Category: Whitlow M]]
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[[Category: Adler, M.]]
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[[Category: Whitlow, M.]]
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[[Category: dimerization]]
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[[Category: heme]]
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[[Category: inhibitor]]
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[[Category: l-arginine monooxygenase]]
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[[Category: nitric oxide]]
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[[Category: no]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:22:14 2008''
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Current revision

Murine Inducible Nitric Oxide Synthase Oxygenase Domain (Delta 114) 1-Benzo[1,3]dioxol-5-ylmethyl-3S-(4-imidazol-1-yl-phenoxy)-piperidine Complex

PDB ID 2ort

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