2ORT
Murine Inducible Nitric Oxide Synthase Oxygenase Domain (Delta 114) 1-Benzo[1,3]dioxol-5-ylmethyl-3S-(4-imidazol-1-yl-phenoxy)-piperidine Complex
Summary for 2ORT
| Entry DOI | 10.2210/pdb2ort/pdb |
| Related | 1DD7 1NOC 1NOD 1NOS 1NSI 2NOS 2ORO 2ORP 2ORQ 2ORR 2ORS |
| Descriptor | Nitric oxide synthase, inducible, PROTOPORPHYRIN IX CONTAINING FE, (3S)-1-(1,3-BENZODIOXOL-5-YLMETHYL)-3-[4-(1H-IMIDAZOL-1-YL)PHENOXY]PIPERIDINE, ... (4 entities in total) |
| Functional Keywords | nitric oxide, l-arginine monooxygenase, heme, dimerization, inhibitor, nos, oxidoreductase |
| Biological source | Mus musculus (house mouse) |
| Total number of polymer chains | 1 |
| Total formula weight | 46264.30 |
| Authors | Adler, M.,Whitlow, M. (deposition date: 2007-02-04, release date: 2007-04-17, Last modification date: 2023-08-30) |
| Primary citation | Davey, D.D.,Adler, M.,Arnaia, D.,Eagen, K.,Erickson, S.,Guilford, W.,Kenrick, M.,Morrissey, M.M.,Ohimeyer, M.,Pan, G.,Paradkar, V.M.,Parkinson, J.,Polokoff, M.,Salonz, K.,Santos, C.,Subramanyam, B.,Vergona, R.,Wei, R.G.,Whitlow, M.,Ye, B.,Zhao, Z.S.,Devlin, J.J.,Phillips, G. Design, Synthesis, and Activity of 2-Imidazol-1-ylpyrimidine Derived Inducible Nitric Oxide Synthase Dimerization Inhibitors J.Med.Chem., 50:1146-1157, 2007 Cited by PubMed Abstract: 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. PubMed: 17315988DOI: 10.1021/jm061319i PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.87 Å) |
Structure validation
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