2orp: Difference between revisions
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==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== | ==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]] 1.97Å' scene=''> | <StructureSection load='2orp' size='340' side='right' caption='[[2orp]], [[Resolution|resolution]] 1.97Å' scene=''> | ||
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<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='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='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> | <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], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2orp ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/or/2orp_consurf.spt"</scriptWhenChecked> | <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> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
Revision as of 09:44, 22 August 2018
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 complexMurine 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
Structural highlights
Function[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.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedBy 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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