[English] 日本語
Yorodumi- PDB-5c2h: PDE10 complexed with 6-chloro-N-[(2,4-dimethylthiazol-5-yl)methyl... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5c2h | ||||||
---|---|---|---|---|---|---|---|
Title | PDE10 complexed with 6-chloro-N-[(2,4-dimethylthiazol-5-yl)methyl]-5-methyl-2-[3-(2-quinolyl)propoxy]pyrimidin-4-amine | ||||||
Components | cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A | ||||||
Keywords | hydrolase/hydrolase inhibitor / Phosphodiesterase / inhibitor / complex / hydrolase-hydrolase inhibitor complex | ||||||
Function / homology | Function and homology information 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 ...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 / FOURIER SYNTHESIS / Resolution: 2.09 Å | ||||||
Authors | Yan, Y. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2015 Title: Discovery and Optimization of a Series of Pyrimidine-Based Phosphodiesterase 10A (PDE10A) Inhibitors through Fragment Screening, Structure-Based Design, and Parallel Synthesis. Authors: Shipe, W.D. / Sharik, S.S. / Barrow, J.C. / McGaughey, G.B. / Theberge, C.R. / Uslaner, J.M. / Yan, Y. / Renger, J.J. / Smith, S.M. / Coleman, P.J. / Cox, C.D. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 5c2h.cif.gz | 143.6 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb5c2h.ent.gz | 110.7 KB | Display | PDB format |
PDBx/mmJSON format | 5c2h.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5c2h_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 5c2h_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | 5c2h_validation.xml.gz | 23.8 KB | Display | |
Data in CIF | 5c2h_validation.cif.gz | 32.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/c2/5c2h ftp://data.pdbj.org/pub/pdb/validation_reports/c2/5c2h | HTTPS FTP |
-Related structure data
Related structure data | 5c1wC 5c28C 5c29C 5c2aC 5c2eC 4zo5S C: citing same article (ref.) S: Starting model for refinement |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
2 |
| ||||||||
Unit cell |
|
-Components
-Protein , 1 types, 2 molecules AB
#1: Protein | Mass: 41495.504 Da / Num. of mol.: 2 / Fragment: catalytic domain Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PDE10A / Production host: Escherichia coli (E. coli) References: UniProt: Q9Y233, 3',5'-cyclic-nucleotide phosphodiesterase, 3',5'-cyclic-GMP phosphodiesterase |
---|
-Non-polymers , 5 types, 68 molecules
#2: Chemical | #3: Chemical | #4: Chemical | ChemComp-4PX / | #5: Chemical | ChemComp-4XU / | #6: Water | ChemComp-HOH / | |
---|
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 1.88 Å3/Da / Density % sol: 34.42 % |
---|---|
Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7.5 Details: 100mM HEPES, 20% PEG3350, 200mM MgCl2, and 10mM 2-Mercaptoethanol |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: May 8, 2009 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.56→50 Å / Num. obs: 88979 / % possible obs: 98.7 % / Redundancy: 6.2 % / Biso Wilson estimate: 19.47 Å2 / Rmerge(I) obs: 0.051 / Χ2: 0.968 / Net I/av σ(I): 28.013 / Net I/σ(I): 15.2 / Num. measured all: 548846 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1 / Rejects: _
|
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: FOURIER SYNTHESIS Starting model: 4ZO5 Resolution: 2.09→36.1 Å / Cor.coef. Fo:Fc: 0.9204 / Cor.coef. Fo:Fc free: 0.8893 / SU R Cruickshank DPI: 0.283 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.281 / SU Rfree Blow DPI: 0.201 / SU Rfree Cruickshank DPI: 0.204
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 123.89 Å2 / Biso mean: 47.13 Å2 / Biso min: 22.83 Å2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine analyze | Luzzati coordinate error obs: 0.309 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.09→36.1 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 2.09→2.15 Å / Total num. of bins used: 17
|