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Yorodumi- PDB-5xkm: Crystal structure of human phosphodiesterase 2A in complex with 6... -
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-Basic information
Entry | Database: PDB / ID: 5xkm | ||||||
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Title | Crystal structure of human phosphodiesterase 2A in complex with 6-methyl-N-(1-(4-(trifluoromethoxy)phenyl)propyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide | ||||||
Components | cGMP-dependent 3',5'-cyclic phosphodiesterase | ||||||
Keywords | HYDROLASE / Hydrolase Inhibitor / PDE2A | ||||||
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 / 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 / monocyte differentiation / 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 / positive regulation of inflammatory response / cellular response to mechanical stimulus / 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 / Golgi apparatus / negative regulation of transcription by RNA polymerase II / magnesium ion binding / endoplasmic reticulum / protein homodimerization activity / zinc ion binding / identical protein binding / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / Resolution: 2.16 Å | ||||||
Authors | Oki, H. / Kondo, M. / Snell, G. / Lane, W. | ||||||
Citation | Journal: J. Med. Chem. / Year: 2017 Title: Discovery of an Orally Bioavailable, Brain-Penetrating, in Vivo Active Phosphodiesterase 2A Inhibitor Lead Series for the Treatment of Cognitive Disorders. Authors: Mikami, S. / Sasaki, S. / Asano, Y. / Ujikawa, O. / Fukumoto, S. / Nakashima, K. / Oki, H. / Kamiguchi, N. / Imada, H. / Iwashita, H. / Taniguchi, T. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5xkm.cif.gz | 428.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5xkm.ent.gz | 349.6 KB | Display | PDB format |
PDBx/mmJSON format | 5xkm.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xk/5xkm ftp://data.pdbj.org/pub/pdb/validation_reports/xk/5xkm | HTTPS FTP |
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-Related structure data
Similar structure data |
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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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Unit cell |
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-Components
#1: Protein | Mass: 40232.051 Da / Num. of mol.: 6 / Fragment: UNP RESIDUES 578-919 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PDE2A / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: O00408, 3',5'-cyclic-nucleotide phosphodiesterase #2: Chemical | ChemComp-MG / #3: Chemical | ChemComp-ZN / #4: Chemical | ChemComp-87R / #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: 2.12 Å3/Da / Density % sol: 41.99 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 7.5 Details: 100 mM tris HCl, pH 7.50, 410 mM magnesium chloride hexahydrate, 29.3%w/v PEG 3350 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.3 / Wavelength: 0.97645 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Sep 8, 2011 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97645 Å / Relative weight: 1 |
Reflection | Resolution: 2.16→84.82 Å / Num. obs: 100556 / % possible obs: 96.8 % / Redundancy: 1.8 % / Net I/σ(I): 8.5 |
-Processing
Software |
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Refinement | Resolution: 2.16→84.82 Å / Cor.coef. Fo:Fc: 0.947 / Cor.coef. Fo:Fc free: 0.913 / SU B: 7.485 / SU ML: 0.186 / Cross valid method: THROUGHOUT / ESU R: 0.37 / ESU R Free: 0.245
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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 mean: 26.626 Å2
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Refinement step | Cycle: 1 / Resolution: 2.16→84.82 Å
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