2orp: Difference between revisions
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New page: left|200px<br /><applet load="2orp" size="450" color="white" frame="true" align="right" spinBox="true" caption="2orp, resolution 1.97Å" /> '''Murine inducible nit... |
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[[Image:2orp.gif|left|200px]]<br /><applet load="2orp" size=" | [[Image:2orp.gif|left|200px]]<br /><applet load="2orp" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="2orp, resolution 1.97Å" /> | caption="2orp, resolution 1.97Å" /> | ||
'''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'''<br /> | '''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'''<br /> | ||
==Overview== | ==Overview== | ||
By the screening of a combinatorial library for inhibitors of nitric oxide | 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. | ||
==About this Structure== | ==About this Structure== | ||
2ORP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with HEM and R86 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | 2ORP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=HEM:'>HEM</scene> and <scene name='pdbligand=R86:'>R86</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ORP OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: nitric oxide; l-arginine monooxygenase; heme; dimerization; inhibitor; nos]] | [[Category: nitric oxide; l-arginine monooxygenase; heme; dimerization; inhibitor; nos]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:21:53 2008'' | ||
