2ort
From Proteopedia
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|PDB= 2ort |SIZE=350|CAPTION= <scene name='initialview01'>2ort</scene>, resolution 1.87Å | |PDB= 2ort |SIZE=350|CAPTION= <scene name='initialview01'>2ort</scene>, resolution 1.87Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <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> |
| - | |ACTIVITY= [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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= Nos2, Inosl ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus]) | |GENE= Nos2, Inosl ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1dd7|1DD7]], [[2oro|2ORO]], [[2orp|2ORP]], [[2orq|2ORQ]], [[2orr|2ORR]], [[2ors|2ORS]], [[1nos|1NOS]], [[1noc|1NOC]], [[2nos|2NOS]], [[1nod|1NOD]], [[1nsi|1NSI]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ort FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ort OCA], [http://www.ebi.ac.uk/pdbsum/2ort PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2ort RCSB]</span> | ||
}} | }} | ||
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[[Category: Adler, M.]] | [[Category: Adler, M.]] | ||
[[Category: Whitlow, M.]] | [[Category: Whitlow, M.]] | ||
| - | [[Category: 342]] | ||
| - | [[Category: HEM]] | ||
[[Category: dimerization]] | [[Category: dimerization]] | ||
[[Category: heme]] | [[Category: heme]] | ||
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[[Category: no]] | [[Category: no]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:22:14 2008'' |
Revision as of 01:22, 31 March 2008
| |||||||
| , resolution 1.87Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | Nos2, Inosl (Mus musculus) | ||||||
| Activity: | Nitric-oxide synthase, with EC number 1.14.13.39 | ||||||
| Related: | 1DD7, 2ORO, 2ORP, 2ORQ, 2ORR, 2ORS, 1NOS, 1NOC, 2NOS, 1NOD, 1NSI
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Murine Inducible Nitric Oxide Synthase Oxygenase Domain (Delta 114) 1-Benzo[1,3]dioxol-5-ylmethyl-3S-(4-imidazol-1-yl-phenoxy)-piperidine Complex
Overview
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
2ORT is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
Reference
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
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