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Yorodumi- PDB-3ntz: Design, Synthesis, Biological Evaluation and X-ray Crystal Struct... -
+Open data
-Basic information
Entry | Database: PDB / ID: 3ntz | ||||||
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Title | Design, Synthesis, Biological Evaluation and X-ray Crystal Structures of Novel Classical 6,5,6-tricyclicbenzo[4,5]thieno[2,3-d]pyrimidines as Dual Thymidylate Synthase and Dihydrofolate Reductase Inhibitors | ||||||
Components | Dihydrofolate reductase | ||||||
Keywords | OXIDOREDUCTASE/OXIDOREDUCTASE INHIBITOR / dihydrofolate reductase / cyclized inhibitors / OXIDOREDUCTASE hDHFR-263-NADPH / Oxidoreductase-Oxidoreductase Inhibitor complex | ||||||
Function / homology | Function and homology information regulation of removal of superoxide radicals / tetrahydrobiopterin biosynthetic process / Metabolism of folate and pterines / tetrahydrofolate metabolic process / sequence-specific mRNA binding / response to methotrexate / dihydrofolate metabolic process / axon regeneration / folic acid binding / G1/S-Specific Transcription ...regulation of removal of superoxide radicals / tetrahydrobiopterin biosynthetic process / Metabolism of folate and pterines / tetrahydrofolate metabolic process / sequence-specific mRNA binding / response to methotrexate / dihydrofolate metabolic process / axon regeneration / folic acid binding / G1/S-Specific Transcription / folic acid metabolic process / glycine biosynthetic process / dihydrofolate reductase / dihydrofolate reductase activity / NADPH binding / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / tetrahydrofolate biosynthetic process / mRNA regulatory element binding translation repressor activity / positive regulation of nitric-oxide synthase activity / one-carbon metabolic process / NADP binding / negative regulation of translation / mRNA binding / mitochondrion / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.35 Å | ||||||
Authors | Cody, V. | ||||||
Citation | Journal: Bioorg.Med.Chem. / Year: 2011 Title: Design, synthesis, biological evaluation and X-ray crystal structure of novel classical 6,5,6-tricyclic benzo[4,5]thieno[2,3-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors. Authors: Zhang, X. / Zhou, X. / Kisliuk, R.L. / Piraino, J. / Cody, V. / Gangjee, A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3ntz.cif.gz | 59.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3ntz.ent.gz | 42.7 KB | Display | PDB format |
PDBx/mmJSON format | 3ntz.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/nt/3ntz ftp://data.pdbj.org/pub/pdb/validation_reports/nt/3ntz | HTTPS FTP |
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-Related 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: 21349.525 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: DHFR, DHFRP1 / Plasmid: pds5 / Production host: Escherichia coli (E. coli) / References: UniProt: P00374, dihydrofolate reductase | ||
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#2: Chemical | ChemComp-3TZ / | ||
#3: Chemical | ChemComp-NDP / | ||
#4: Chemical | ChemComp-SO4 / #5: 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: 2.49 Å3/Da / Density % sol: 50.62 % |
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Crystal grow | Temperature: 293 K / pH: 6.9 Details: 100 mM KPO4, 66% saturated AmSO4, 3% v/v ethanol, pH 6.9, VAPOR DIFFUSION, HANGING DROP, temperature 200K, temperature 293K |
-Data collection
Diffraction | Mean temperature: 200 K |
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Diffraction source | Source: SYNCHROTRON / Site: SSRL / Beamline: BL9-2 / Wavelength: 0.975 |
Detector | Type: MARMOSAIC 325 mm CCD / Detector: CCD / Date: Dec 6, 2008 / Details: MIRRORS |
Radiation | Monochromator: GRAPHITE / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.975 Å / Relative weight: 1 |
Reflection | Resolution: 1.35→53.22 Å / Num. obs: 45260 / % possible obs: 100 % / Observed criterion σ(I): 2 / Redundancy: 3.7 % / Rmerge(I) obs: 0.053 / Rsym value: 0.03 / Net I/σ(I): 15.3 |
Reflection shell | Resolution: 1.35→1.42 Å / Redundancy: 3.7 % / Rmerge(I) obs: 0.61 / Mean I/σ(I) obs: 1.6 / Rsym value: 0.36 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: U072 Resolution: 1.35→26.61 Å / Cor.coef. Fo:Fc: 0.967 / Cor.coef. Fo:Fc free: 0.962 / SU B: 0.976 / SU ML: 0.04 / Isotropic thermal model: isotropic / Cross valid method: THROUGHOUT / ESU R: 0.058 / ESU R Free: 0.057 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 18.91 Å2
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Refine analyze | Luzzati sigma a obs: 0.159 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.35→26.61 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.35→1.39 Å / Total num. of bins used: 20
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