2orp: Difference between revisions
No edit summary |
No edit summary |
||
| Line 2: | Line 2: | ||
<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=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2orp]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <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> | </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='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 | <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- | <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://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]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| Line 29: | Line 29: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 2orp" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
| Line 36: | Line 37: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Lk3 transgenic mice]] | ||
[[Category: Adler, M]] | [[Category: Adler, M]] | ||
[[Category: Whitlow, M]] | [[Category: Whitlow, M]] | ||
Revision as of 05:13, 11 September 2015
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
|
| ||||||||||||||||||||||