+Open data
-Basic information
Entry | Database: PDB / ID: 4ael | ||||||
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Title | PDE10A in complex with the inhibitor AZ5 | ||||||
Components | CAMP AND CAMP-INHIBITED CGMP 3', 5'-CYCLIC PHOSPHODIESTERASE 10A | ||||||
Keywords | HYDROLASE / HIT-TO-LEAD / ENZYME INHIBITOR / NAPHTYRIDINE | ||||||
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: 2.2 Å | ||||||
Authors | Bauer, U. / Giordanetto, F. / Bauer, M. / OMahony, G. / Johansson, K.E. / Knecht, W. / Hartleib-Geschwindner, J. / Toppner Carlsson, E. / Enroth, C. / Sjogren, T. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2012 Title: Discovery of 4-Hydroxy-1,6-Naphthyridine-3-Carbonitrile Derivatives as Novel Pde10A Inhibitors. Authors: Bauer, U. / Giordanetto, F. / Bauer, M. / O'Mahony, G. / Johansson, K.E. / Knecht, W. / Hartleib-Geschwindner, J. / Carlsson, E.T. / Enroth, C. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4ael.cif.gz | 150.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4ael.ent.gz | 117.8 KB | Display | PDB format |
PDBx/mmJSON format | 4ael.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4ael_validation.pdf.gz | 1006.5 KB | Display | wwPDB validaton report |
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Full document | 4ael_full_validation.pdf.gz | 1009.8 KB | Display | |
Data in XML | 4ael_validation.xml.gz | 27.4 KB | Display | |
Data in CIF | 4ael_validation.cif.gz | 39.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ae/4ael ftp://data.pdbj.org/pub/pdb/validation_reports/ae/4ael | HTTPS FTP |
-Related structure data
Related structure data | 2oupS 2y5u 2y5v 2y5x 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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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 39465.215 Da / Num. of mol.: 2 / Fragment: CATALYTIC DOMAIN, RESIDUES 438-779 Source method: isolated from a genetically manipulated source Source: (gene. exp.) HOMO SAPIENS (human) / Production host: ESCHERICHIA COLI (E. coli) References: UniProt: Q9Y233, 3',5'-cyclic-nucleotide phosphodiesterase, 3',5'-cyclic-GMP phosphodiesterase #2: Chemical | #3: Chemical | #4: Chemical | #5: Water | ChemComp-HOH / | Nonpolymer details | 2-(2'-ETHOXYBIPHENYL-4-YL)-4-HYDROXY-1, 6-NAPHTHYRIDINE-3-CARBONITRILE (4HN): HET COMPOUND ALIAS IN ...2-(2'-ETHOXYBIPH | Sequence details | THE FIRST THREE RESIDUES ORIGINATES | |
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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: 2.14 Å3/Da / Density % sol: 42.4 % / Description: NONE |
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Crystal grow | pH: 7.5 Details: 20 MM TRIS PH 7.5, 100 MM NACL AND 10 MM BETA MERCAPTOETHANOL |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: ID29 / Wavelength: 0.98 |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Aug 26, 2008 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.98 Å / Relative weight: 1 |
Reflection | Resolution: 2.2→40 Å / Num. obs: 30061 / % possible obs: 88.4 % / Observed criterion σ(I): 2 / Redundancy: 4.5 % / Rmerge(I) obs: 0.06 / Net I/σ(I): 13.4 |
Reflection shell | Resolution: 2.2→2.26 Å / Redundancy: 4.7 % / Rmerge(I) obs: 0.36 / Mean I/σ(I) obs: 4.1 / % possible all: 83 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 2OUP Resolution: 2.2→50 Å / Cor.coef. Fo:Fc: 0.954 / Cor.coef. Fo:Fc free: 0.935 / Cross valid method: THROUGHOUT / ESU R: 0.461 / ESU R Free: 0.258 / 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: 43.49 Å2
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Refinement step | Cycle: LAST / Resolution: 2.2→50 Å
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