2ort

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{{Seed}}
 
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[[Image:2ort.png|left|200px]]
 
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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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The line below this paragraph, containing "STRUCTURE_2ort", creates the "Structure Box" on the page.
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<StructureSection load='2ort' size='340' side='right'caption='[[2ort]], [[Resolution|resolution]] 1.87&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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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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or leave the SCENE parameter empty for the default display.
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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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<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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{{STRUCTURE_2ort| PDB=2ort | SCENE= }}
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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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</table>
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== Function ==
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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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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_17315988}}, adds the Publication Abstract to the page
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*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 17315988 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_17315988}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[Category: Large Structures]]
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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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==Reference==
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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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The rational design of inhibitors of nitric oxide formation by inducible nitric oxide synthase., Whitlow M, Adler M, Davey D, Huang Q, Koovakkat S, Parkinson JF, Pham E, Polokoff M, Xu W, Yuan S, Phillips G, Bioorg Med Chem Lett. 2007 May 1;17(9):2505-8. Epub 2007 Feb 9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17336523 17336523]
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Allosteric inhibitors of inducible nitric oxide synthase dimerization discovered via combinatorial chemistry., McMillan K, Adler M, Auld DS, Baldwin JJ, Blasko E, Browne LJ, Chelsky D, Davey D, Dolle RE, Eagen KA, Erickson S, Feldman RI, Glaser CB, Mallari C, Morrissey MM, Ohlmeyer MH, Pan G, Parkinson JF, Phillips GB, Polokoff MA, Sigal NH, Vergona R, Whitlow M, Young TA, Devlin JJ, Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1506-11. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10677491 10677491]
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The structure of nitric oxide synthase oxygenase domain and inhibitor complexes., Crane BR, Arvai AS, Gachhui R, Wu C, Ghosh DK, Getzoff ED, Stuehr DJ, Tainer JA, Science. 1997 Oct 17;278(5337):425-31. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9334294 9334294]
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Characterization of the inducible nitric oxide synthase oxygenase domain identifies a 49 amino acid segment required for subunit dimerization and tetrahydrobiopterin interaction., Ghosh DK, Wu C, Pitters E, Moloney M, Werner ER, Mayer B, Stuehr DJ, Biochemistry. 1997 Sep 2;36(35):10609-19. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9271491 9271491]
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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 Tue Jul 29 14:58:40 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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