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Yorodumi- PDB-5tzc: Crystal Structure of human PDE2a in complex with (5S)-1-[(3-bromo... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5tzc | ||||||
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Title | Crystal Structure of human PDE2a in complex with (5S)-1-[(3-bromo-4-fluorophenyl)carbonyl]-3,3-difluoro-5-{5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl}piperidine | ||||||
Components | cGMP-dependent 3',5'-cyclic phosphodiesterase | ||||||
Keywords | Hydrolase/Hydrolase Inhibitor / phosphodiesterase / Hydrolase-Hydrolase Inhibitor complex | ||||||
Function / homology | Function and homology information regulation of cGMP-mediated signaling / cellular response to 2,3,7,8-tetrachlorodibenzodioxine / cellular response to macrophage colony-stimulating factor stimulus / cellular response to cGMP / negative regulation of cAMP-mediated signaling / negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of vascular permeability / heart valve development / cellular response to granulocyte macrophage colony-stimulating factor stimulus / negative regulation of vascular permeability ...regulation of cGMP-mediated signaling / cellular response to 2,3,7,8-tetrachlorodibenzodioxine / cellular response to macrophage colony-stimulating factor stimulus / cellular response to cGMP / negative regulation of cAMP-mediated signaling / negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of vascular permeability / heart valve development / cellular response to granulocyte macrophage colony-stimulating factor stimulus / negative regulation of vascular permeability / establishment of endothelial barrier / monocyte differentiation / regulation of mitochondrion organization / aorta development / ventricular septum development / 3',5'-cGMP-stimulated cyclic-nucleotide phosphodiesterase activity / 3',5'-cyclic-nucleotide phosphodiesterase / negative regulation of cGMP-mediated signaling / TPR domain binding / cGMP-mediated signaling / cGMP catabolic process / phosphate ion binding / cGMP effects / cGMP binding / 3',5'-cyclic-GMP phosphodiesterase activity / 3',5'-cyclic-AMP phosphodiesterase activity / regulation of cAMP-mediated signaling / cAMP binding / cellular response to cAMP / cellular response to transforming growth factor beta stimulus / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / cAMP-mediated signaling / synaptic membrane / cellular response to mechanical stimulus / positive regulation of inflammatory response / cellular response to xenobiotic stimulus / presynaptic membrane / G alpha (s) signalling events / mitochondrial outer membrane / mitochondrial inner membrane / mitochondrial matrix / positive regulation of gene expression / perinuclear region of cytoplasm / negative regulation of transcription by RNA polymerase II / magnesium ion binding / Golgi apparatus / endoplasmic reticulum / protein homodimerization activity / zinc ion binding / identical protein binding / nucleus / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.36 Å | ||||||
Authors | Xu, R. / Aertgeerts, K. | ||||||
Citation | Journal: J. Med. Chem. / Year: 2017 Title: Design and Synthesis of Novel and Selective Phosphodiesterase 2 (PDE2a) Inhibitors for the Treatment of Memory Disorders. Authors: Gomez, L. / Massari, M.E. / Vickers, T. / Freestone, G. / Vernier, W. / Ly, K. / Xu, R. / McCarrick, M. / Marrone, T. / Metz, M. / Yan, Y.G. / Yoder, Z.W. / Lemus, R. / Broadbent, N.J. / ...Authors: Gomez, L. / Massari, M.E. / Vickers, T. / Freestone, G. / Vernier, W. / Ly, K. / Xu, R. / McCarrick, M. / Marrone, T. / Metz, M. / Yan, Y.G. / Yoder, Z.W. / Lemus, R. / Broadbent, N.J. / Barido, R. / Warren, N. / Schmelzer, K. / Neul, D. / Lee, D. / Andersen, C.B. / Sebring, K. / Aertgeerts, K. / Zhou, X. / Tabatabaei, A. / Peters, M. / Breitenbucher, J.G. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5tzc.cif.gz | 552.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5tzc.ent.gz | 453.3 KB | Display | PDB format |
PDBx/mmJSON format | 5tzc.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5tzc_validation.pdf.gz | 1.7 MB | Display | wwPDB validaton report |
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Full document | 5tzc_full_validation.pdf.gz | 1.7 MB | Display | |
Data in XML | 5tzc_validation.xml.gz | 49 KB | Display | |
Data in CIF | 5tzc_validation.cif.gz | 66.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/tz/5tzc ftp://data.pdbj.org/pub/pdb/validation_reports/tz/5tzc | HTTPS FTP |
-Related structure data
Related structure data | 5tz3C 5tzaC 5tzhC 5tzwC 5tzxC 5tzzC 5u00C C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Component-ID: _ / Refine code: _
NCS ensembles :
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-Components
#1: Protein | Mass: 40168.051 Da / Num. of mol.: 4 / Fragment: catalytic domain, UNP residues 323-663 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PDE2A / Production host: Trichoplusia ni (cabbage looper) / Strain (production host): baculovirus insect cell Hi5 References: UniProt: O00408, 3',5'-cyclic-nucleotide phosphodiesterase #2: Chemical | ChemComp-7OJ / ( #3: Chemical | ChemComp-ZN / #4: Chemical | ChemComp-MG / #5: Water | ChemComp-HOH / | |
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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: 2.2 Å3/Da / Density % sol: 44.01 % / Mosaicity: 0.648 ° / Mosaicity esd: 0.01 ° |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 8.4 / Details: 17-19% PEG3350, 0.2M MgCl2, 0.1M Tris, pH 8.4 |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 0.9761 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Jul 31, 2013 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9761 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.35→50 Å / Num. obs: 55551 / % possible obs: 98.5 % / Redundancy: 2.1 % / Rmerge(I) obs: 0.105 / Rpim(I) all: 0.098 / Rrim(I) all: 0.144 / Χ2: 1.052 / Net I/av σ(I): 7.958 / Net I/σ(I): 6.1 / Num. measured all: 116391 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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-Phasing
Phasing | Method: molecular replacement | |||||||||
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Phasing MR | Model details: Phaser MODE: MR_AUTO
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.36→46.81 Å / Cor.coef. Fo:Fc: 0.935 / Cor.coef. Fo:Fc free: 0.902 / SU B: 17.305 / SU ML: 0.196 / SU R Cruickshank DPI: 0.6271 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.627 / ESU R Free: 0.27 Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 137.48 Å2 / Biso mean: 30.215 Å2 / Biso min: 2.94 Å2
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Refinement step | Cycle: final / Resolution: 2.36→46.81 Å
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Refine LS restraints |
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Refine LS restraints NCS | Refine-ID: X-RAY DIFFRACTION / Type: interatomic distance / Weight position: 0.05
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LS refinement shell | Resolution: 2.356→2.417 Å / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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