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Open data
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Basic information
Entry | Database: PDB / ID: 6zqz | ||||||
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Title | [1,2,4]Triazolo[1,5-a]pyrimidine Phosphodiesterase 2 Inhibitors | ||||||
![]() | cGMP-dependent 3',5'-cyclic phosphodiesterase | ||||||
![]() | HYDROLASE / PDE2A inhibitor / FEP / SBDD / Free energy perturbation / molecular dynamics / Alzheimers disease / phosphodiesterase / molecular design / binding free energy | ||||||
Function / homology | ![]() 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 | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Tresadern, G. / Leonard, P.M. | ||||||
![]() | ![]() Title: [1,2,4]Triazolo[1,5- a ]pyrimidine Phosphodiesterase 2A Inhibitors: Structure and Free-Energy Perturbation-Guided Exploration. Authors: Tresadern, G. / Velter, I. / Trabanco, A.A. / Van den Keybus, F. / Macdonald, G.J. / Somers, M.V.F. / Vanhoof, G. / Leonard, P.M. / Lamers, M.B.A.C. / Van Roosbroeck, Y.E.M. / Buijnsters, P.J.J.A. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 298.4 KB | Display | ![]() |
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PDB format | ![]() | 237.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 6zndC ![]() 1z1lS S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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2 | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 41432.375 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: O00408, 3',5'-cyclic-nucleotide phosphodiesterase #2: Chemical | ChemComp-ZN / #3: Chemical | ChemComp-MG / #4: Chemical | ChemComp-QOQ / #5: Water | ChemComp-HOH / | Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.16 Å3/Da / Density % sol: 43.04 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 8 Details: 0.2 M MgCl2, 0.1 M Tris-HCl pH 8.0 and 24 % PEG 3350 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Aug 11, 2011 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9795 Å / Relative weight: 1 |
Reflection | Resolution: 1.88→87.07 Å / Num. obs: 105695 / % possible obs: 93.4 % / Redundancy: 1.7 % / Rmerge(I) obs: 0.067 / Net I/σ(I): 7 |
Reflection shell | Resolution: 1.88→1.93 Å / Rmerge(I) obs: 0.261 / Mean I/σ(I) obs: 2.2 / Num. unique obs: 10569 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 1z1l Resolution: 1.88→87.07 Å / Cor.coef. Fo:Fc: 0.942 / Cor.coef. Fo:Fc free: 0.911 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.181 / ESU R Free: 0.164 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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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: 57.3 Å2 / Biso mean: 18.672 Å2 / Biso min: 7.5 Å2
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Refinement step | Cycle: final / Resolution: 1.88→87.07 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.88→1.927 Å / Rfactor Rfree error: 0
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