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Yorodumi- PDB-2ort: Murine Inducible Nitric Oxide Synthase Oxygenase Domain (Delta 11... -
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-Basic information
Entry | Database: PDB / ID: 2ort | ||||||
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Title | Murine Inducible Nitric Oxide Synthase Oxygenase Domain (Delta 114) 1-Benzo[1,3]dioxol-5-ylmethyl-3S-(4-imidazol-1-yl-phenoxy)-piperidine Complex | ||||||
Components | Nitric oxide synthase, inducible | ||||||
Keywords | OXIDOREDUCTASE / NITRIC OXIDE / L-ARGININE MONOOXYGENASE / HEME / DIMERIZATION / INHIBITOR / NOS | ||||||
Function / homology | Function and homology information Nitric oxide stimulates guanylate cyclase / ROS and RNS production in phagocytes / G protein-coupled receptor signaling pathway coupled to cGMP nucleotide second messenger / Peroxisomal protein import / cAMP-dependent protein kinase regulator activity / positive regulation of killing of cells of another organism / prostaglandin secretion / tetrahydrobiopterin binding / arginine binding / cortical cytoskeleton ...Nitric oxide stimulates guanylate cyclase / ROS and RNS production in phagocytes / G protein-coupled receptor signaling pathway coupled to cGMP nucleotide second messenger / Peroxisomal protein import / cAMP-dependent protein kinase regulator activity / positive regulation of killing of cells of another organism / prostaglandin secretion / tetrahydrobiopterin binding / arginine binding / cortical cytoskeleton / superoxide metabolic process / cGMP-mediated signaling / nitric-oxide synthase binding / peptidyl-cysteine S-nitrosylation / regulation of cytokine production involved in inflammatory response / cellular response to cytokine stimulus / regulation of insulin secretion / cellular response to organic cyclic compound / nitric-oxide synthase (NADPH) / blood vessel remodeling / nitric oxide mediated signal transduction / response to tumor necrosis factor / nitric-oxide synthase activity / arginine catabolic process / nitric oxide biosynthetic process / negative regulation of blood pressure / response to hormone / positive regulation of interleukin-8 production / negative regulation of protein catabolic process / response to bacterium / regulation of blood pressure / Hsp90 protein binding / circadian rhythm / cellular response to type II interferon / beta-catenin binding / positive regulation of interleukin-6 production / cellular response to xenobiotic stimulus / FMN binding / peroxisome / NADP binding / flavin adenine dinucleotide binding / actin binding / regulation of cell population proliferation / cellular response to lipopolysaccharide / response to lipopolysaccharide / calmodulin binding / response to hypoxia / intracellular signal transduction / defense response to bacterium / cadherin binding / inflammatory response / positive regulation of apoptotic process / negative regulation of gene expression / heme binding / protein kinase binding / perinuclear region of cytoplasm / protein homodimerization activity / extracellular space / identical protein binding / nucleus / metal ion binding / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Mus musculus (house mouse) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 1.87 Å | ||||||
Authors | Adler, M. / Whitlow, M. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2007 Title: Design, Synthesis, and Activity of 2-Imidazol-1-ylpyrimidine Derived Inducible Nitric Oxide Synthase Dimerization Inhibitors Authors: 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. / ...Authors: 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. #1: Journal: Bioorg.Med.Chem.Lett. / Year: 2007 Title: The Rational Design of Inhibitors of Nitric Oxide Formation by Inducible Nitric Oxide Synthase Authors: Whitlow, M. / Adler, M. / Davey, D.D. / Huang, Q. / Koovakkat, S. / Pham, E. / Polokoff, M. / Xu, W. / Yuan, S.S. / Phillips, G. #2: Journal: To be Published / Year: 2007 Title: 3-[4-(1-Imidazolyl)phenoxy]-1-piperonyl Piperidine Analogs as Potent and Selective Inhibitors of Nitric Oxide Formation Authors: Wei, R.G. / Adler, M. / Davey, D. / Ho, E. / Mohan, R. / Polokoff, M. / Tseng, J.L. / Whitlow, M. / Xu, W. / Yuan, S. / Phillips, G. #3: Journal: Proc.Natl.Acad.Sci.USA / Year: 2000 Title: Allosteric inhibitors of inducible nitric oxide synthase dimerization discovered via combinatorial chemistry. Authors: McMillan, K. / Adler, M. / Auld, D.S. / Baldwin, J.J. / Blasko, E. / Browne, L.J. / Chelsky, D. / Davey, D. / Dolle, R.E. / Eagen, K.A. / Erickson, S. / Feldman, R.I. / Glaser, C.B. / ...Authors: McMillan, K. / Adler, M. / Auld, D.S. / Baldwin, J.J. / Blasko, E. / Browne, L.J. / Chelsky, D. / Davey, D. / Dolle, R.E. / Eagen, K.A. / Erickson, S. / Feldman, R.I. / Glaser, C.B. / Mallari, C. / Morrissey, M.M. / Ohlmeyer, M.H. / Pan, G. / Parkinson, J.F. / Phillips, G.B. / Polokoff, M.A. / Sigal, N.H. / Vergona, R. / Whitlow, M. / Young, T.A. / Devlin, J.J. #4: Journal: Science / Year: 1997 Title: The structure of nitric oxide synthase oxygenase domain and inhibitor complexes. Authors: Crane, B.R. / Arvai, A.S. / Gachhui, R. / Wu, C. / Ghosh, D.K. / Getzoff, E.D. / Stuehr, D.J. / Tainer, J.A. #5: Journal: Biochemistry / Year: 1997 Title: Characterization of the inducible nitric oxide synthase oxygenase domain identifies a 49 amino acid segment required for subunit dimerization and tetrahydrobiopterin interaction. Authors: Ghosh, D.K. / Wu, C. / Pitters, E. / Moloney, M. / Werner, E.R. / Mayer, B. / Stuehr, D.J. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 2ort.cif.gz | 87.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb2ort.ent.gz | 63.3 KB | Display | PDB format |
PDBx/mmJSON format | 2ort.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 2ort_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 2ort_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 2ort_validation.xml.gz | 16.3 KB | Display | |
Data in CIF | 2ort_validation.cif.gz | 23.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/or/2ort ftp://data.pdbj.org/pub/pdb/validation_reports/or/2ort | HTTPS FTP |
-Related structure data
Related structure data | 2oroC 2orpC 2orqC 2orrC 2orsC 1nosS C: citing same article (ref.) S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 45270.379 Da / Num. of mol.: 1 / Fragment: OXYGENASE DOMAIN 114-498 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Gene: Nos2, Inosl / Plasmid: PCWORI / Production host: Escherichia coli (E. coli) / References: UniProt: P29477, nitric-oxide synthase (NADPH) |
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#2: Chemical | ChemComp-HEM / |
#3: Chemical | ChemComp-342 / ( |
#4: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.37 Å3/Da / Density % sol: 48.09 % |
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Crystal grow | Temperature: 308 K / Method: vapor diffusion, hanging drop / pH: 4.7 Details: CRYSTALS OF MURINE DELTA114 INOS WERE PREPARED IN THE PRESENCE OF IMIDAZOLE FOLLOWING THE PROCEDURES OF CRANE ET AL. (REFERENCE 4) AS FOLLOWS: THE 6 UL CRYSTALLIZATION DROPS CONTAINED 20 ...Details: CRYSTALS OF MURINE DELTA114 INOS WERE PREPARED IN THE PRESENCE OF IMIDAZOLE FOLLOWING THE PROCEDURES OF CRANE ET AL. (REFERENCE 4) AS FOLLOWS: THE 6 UL CRYSTALLIZATION DROPS CONTAINED 20 MG/ML MURINE DELTA114 INOS, 20 MM HEPES PH 7.6, 5 % GLYCEROL, 0.5 MM DTT, 6.8 % PEG-3350, 60 MM NA2SO3, AND 50 MM IMIDAZOLE/ MALATE BUFFER PH 4.7 WERE PLACED OVER A 1 ML RESERVOIR CONTAINING 13.6 % PEG-3350, 120 MM NA2SO3, AND 100 MM IMIDAZOLE/MALATE BUFFER PH 4.7. THESE CRYSTALS WERE SOAKED FOR 25 HOURS IN 5 UM 1-Benzo[1,3]dioxol-5-ylmethyl- 3-(4-imidazol-1-yl-phenoxy)-piperidine, 14 % PEG-3350, 1 MM NAN3, 50 MM MES PH 6.5 AND 50 MM NA2SO3. THE, pH 4.70, VAPOR DIFFUSION, HANGING DROP, temperature 308K |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1 / Wavelength: 1 Å | |||||||||
Detector | Type: ADSC QUANTUM 4 / Detector: CCD / Date: Aug 11, 1998 | |||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||
Radiation wavelength |
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Reflection | Resolution: 1.87→29.85 Å / Num. obs: 33816 / % possible obs: 93.2 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 3 % / Biso Wilson estimate: 23.9 Å2 / Rsym value: 0.0606 / Net I/σ(I): 17.9 | |||||||||
Reflection shell | Resolution: 1.87→1.99 Å / Redundancy: 1.94 % / Rmerge(I) obs: 0.2446 / Mean I/σ(I) obs: 2.4 / % possible all: 69 |
-Processing
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Refinement | Method to determine structure: FOURIER SYNTHESIS Starting model: PDB ENTRY 1NOS Resolution: 1.87→29.85 Å / Rfactor Rfree error: 0.007 / Data cutoff high absF: 137140.66 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 2 / Stereochemistry target values: Engh & Huber Details: ATOMS WITH NO 1.0 SIGMA 2FO-FC DENSITY HAD THEIR OCCUPANCY LOWERED TO 0.5. THE POSITION OF THESE ATOMS SHOULD NOT BE TRUSTED.
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Solvent computation | Solvent model: FLAT MODEL / Bsol: 61.7058 Å2 / ksol: 0.347073 e/Å3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 44.2 Å2
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Refine analyze |
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Refinement step | Cycle: LAST / Resolution: 1.87→29.85 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 8
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Xplor file |
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