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Yorodumi- PDB-5si4: Crystal Structure of human phosphodiesterase 10 in complex with 3... -
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-Basic information
Entry | Database: PDB / ID: 5si4 | ||||||
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Title | Crystal Structure of human phosphodiesterase 10 in complex with 3-(2-naphthalen-1-ylpyrazol-3-yl)-1-[3-(trifluoromethoxy)phenyl]pyridazin-4-one | ||||||
Components | cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A | ||||||
Keywords | HYDROLASE/HYDROLASE inhibitor / PHOSPHODIESTERASE / PDE10 / HYDROLASE / SCHIZOPHRENIA / HYDROLASE-HYDROLASE inhibitor complex | ||||||
Function / homology | Function and homology information 3',5'-cGMP-stimulated cyclic-nucleotide phosphodiesterase activity / 3',5'-cyclic-nucleotide phosphodiesterase / negative regulation of cGMP-mediated signaling / cGMP catabolic process / cGMP effects / cAMP catabolic process / 3',5'-cyclic-nucleotide phosphodiesterase activity / cGMP binding / 3',5'-cyclic-GMP phosphodiesterase activity / 3',5'-cyclic-AMP phosphodiesterase activity ...3',5'-cGMP-stimulated cyclic-nucleotide phosphodiesterase activity / 3',5'-cyclic-nucleotide phosphodiesterase / negative regulation of cGMP-mediated signaling / cGMP catabolic process / cGMP effects / cAMP catabolic process / 3',5'-cyclic-nucleotide phosphodiesterase activity / cGMP binding / 3',5'-cyclic-GMP phosphodiesterase activity / 3',5'-cyclic-AMP phosphodiesterase activity / cAMP binding / cAMP-mediated signaling / G alpha (s) signalling events / metal ion binding / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.39 Å | ||||||
Authors | Joseph, C. / Benz, J. / Flohr, A. / Rogers-Evans, M. / Rudolph, M.G. | ||||||
Funding support | Switzerland, 1items
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Citation | Journal: To be published Title: Crystal Structure of a human phosphodiesterase 10 complex Authors: Flohr, A. / Schlatter, D. / Kuhn, B. / Rudolph, M.G. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5si4.cif.gz | 278.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5si4.ent.gz | 225.8 KB | Display | PDB format |
PDBx/mmJSON format | 5si4.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/si/5si4 ftp://data.pdbj.org/pub/pdb/validation_reports/si/5si4 | HTTPS FTP |
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-Group deposition
ID | G_1002229 (175 entries) |
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Title | To be published |
Type | undefined |
Description | A set of PDE10 crystal structures |
-Related structure data
Similar structure data | Similarity search - Function & homologyF&H Search |
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-Links
-Assembly
Deposited unit |
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1 |
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2 |
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3 |
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4 |
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Unit cell |
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-Components
#1: Protein | Mass: 39413.203 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PDE10A / Plasmid: PET28a(+) / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3)pLysS References: UniProt: Q9Y233, 3',5'-cyclic-nucleotide phosphodiesterase #2: Chemical | ChemComp-ZN / #3: Chemical | ChemComp-MG / #4: Chemical | ChemComp-JLR / #5: Water | ChemComp-HOH / | Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.65 Å3/Da / Density % sol: 53.66 % |
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Crystal grow | Temperature: 295 K / Method: vapor diffusion, sitting drop / pH: 7.5 Details: 5-20 mg/mL protein in 25mM HEPES/NaOH pH7.5, 150mM NaCl, 50mM BME mixed 1:1 with reservoir 0.1M HEPES/NaOH pH7.5, 30% PEG550MME, 50mM MgCl2 |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 0.65 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Jul 18, 2008 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.65 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.39→43.75 Å / Num. obs: 64217 / % possible obs: 100 % / Redundancy: 5.792 % / Biso Wilson estimate: 54.446 Å2 / CC1/2: 0.997 / Rmerge(I) obs: 0.131 / Rrim(I) all: 0.144 / Χ2: 0.829 / Net I/σ(I): 11.57 / Num. measured all: 371928 / Scaling rejects: 53 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: inhouse model Resolution: 2.39→43.73 Å / Cor.coef. Fo:Fc: 0.964 / Cor.coef. Fo:Fc free: 0.931 / SU B: 10.144 / SU ML: 0.217 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.344 / ESU R Free: 0.246 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: three out of four copies in the asymmetric unit have an alternative conformation of the ligand bound where the trifluoromethoxyphenyl group is rotated by 180deg. the naphtyl group comes ...Details: three out of four copies in the asymmetric unit have an alternative conformation of the ligand bound where the trifluoromethoxyphenyl group is rotated by 180deg. the naphtyl group comes close to the second position of the trifluoro-group, suggesting a link for a macrocyclic inhibitor.;
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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 max: 137.2 Å2 / Biso mean: 47.153 Å2 / Biso min: 20.39 Å2
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Refinement step | Cycle: final / Resolution: 2.39→43.73 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.386→2.448 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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