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Yorodumi- PDB-6hwo: Crystal structure of human phosphodiesterase 4D2 catalytic domain... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6hwo | ||||||
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Title | Crystal structure of human phosphodiesterase 4D2 catalytic domain with inhibitor NPD-1335 | ||||||
Components | cAMP-specific 3',5'-cyclic phosphodiesterase 4D | ||||||
Keywords | HYDROLASE / phosphodiesterase / cAMP hydrolysis / alternative splicing | ||||||
Function / homology | Function and homology information signaling receptor regulator activity / negative regulation of heart contraction / negative regulation of relaxation of cardiac muscle / 3',5'-cyclic-AMP phosphodiesterase / positive regulation of interleukin-5 production / negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / establishment of endothelial barrier / regulation of cardiac muscle cell contraction / beta-2 adrenergic receptor binding / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel ...signaling receptor regulator activity / negative regulation of heart contraction / negative regulation of relaxation of cardiac muscle / 3',5'-cyclic-AMP phosphodiesterase / positive regulation of interleukin-5 production / negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / establishment of endothelial barrier / regulation of cardiac muscle cell contraction / beta-2 adrenergic receptor binding / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / voltage-gated calcium channel complex / heterocyclic compound binding / positive regulation of heart rate / adrenergic receptor signaling pathway / regulation of cell communication by electrical coupling involved in cardiac conduction / negative regulation of peptidyl-serine phosphorylation / cAMP catabolic process / 3',5'-cyclic-nucleotide phosphodiesterase activity / DARPP-32 events / 3',5'-cyclic-GMP phosphodiesterase activity / calcium channel regulator activity / 3',5'-cyclic-AMP phosphodiesterase activity / cAMP binding / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / cellular response to cAMP / cAMP-mediated signaling / calcium channel complex / cellular response to epinephrine stimulus / positive regulation of interleukin-2 production / regulation of heart rate / positive regulation of type II interferon production / T cell receptor signaling pathway / ATPase binding / scaffold protein binding / G alpha (s) signalling events / transmembrane transporter binding / apical plasma membrane / centrosome / perinuclear region of cytoplasm / enzyme binding / membrane / nucleus / metal ion binding / plasma membrane / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.99 Å | ||||||
Authors | Singh, A.K. / Brown, D.G. | ||||||
Funding support | 1items
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Citation | Journal: Bioorg.Med.Chem. / Year: 2019 Title: Alkynamide phthalazinones as a new class of TbrPDEB1 inhibitors (Part 2). Authors: de Heuvel, E. / Singh, A.K. / Boronat, P. / Kooistra, A.J. / van der Meer, T. / Sadek, P. / Blaazer, A.R. / Shaner, N.C. / Bindels, D.S. / Caljon, G. / Maes, L. / Sterk, G.J. / Siderius, M. ...Authors: de Heuvel, E. / Singh, A.K. / Boronat, P. / Kooistra, A.J. / van der Meer, T. / Sadek, P. / Blaazer, A.R. / Shaner, N.C. / Bindels, D.S. / Caljon, G. / Maes, L. / Sterk, G.J. / Siderius, M. / Oberholzer, M. / de Esch, I.J.P. / Brown, D.G. / Leurs, R. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6hwo.cif.gz | 300.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6hwo.ent.gz | 241.3 KB | Display | PDB format |
PDBx/mmJSON format | 6hwo.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6hwo_validation.pdf.gz | 1.8 MB | Display | wwPDB validaton report |
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Full document | 6hwo_full_validation.pdf.gz | 1.8 MB | Display | |
Data in XML | 6hwo_validation.xml.gz | 57.6 KB | Display | |
Data in CIF | 6hwo_validation.cif.gz | 80.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/hw/6hwo ftp://data.pdbj.org/pub/pdb/validation_reports/hw/6hwo | HTTPS FTP |
-Related structure data
Related structure data | 6gxqC 6rb6C 6rcwC 6rfnC 6rfwC 6rgkC 3sl3S C: citing same article (ref.) 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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3 |
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4 |
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Unit cell |
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-Components
-Protein , 1 types, 4 molecules ABCD
#1: Protein | Mass: 41808.242 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Details: residues 381-740 / Source: (gene. exp.) Homo sapiens (human) / Gene: PDE4D, DPDE3 / Plasmid: pET15b / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): codon plus References: UniProt: Q08499, 3',5'-cyclic-AMP phosphodiesterase |
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-Non-polymers , 8 types, 665 molecules
#2: Chemical | ChemComp-EDO / #3: Chemical | ChemComp-PEG / #4: Chemical | ChemComp-ZN / #5: Chemical | ChemComp-FFZ / #6: Chemical | ChemComp-MG / #7: Chemical | ChemComp-EPE / #8: Chemical | #9: 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: 2.62 Å3/Da / Density % sol: 53.1 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7.5 Details: 24% PEG 3350, 30% Ethylene Glycol, 0.1 M HEPES pH 7.5 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I04-1 / Wavelength: 0.91587 Å |
Detector | Type: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Feb 16, 2018 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.91587 Å / Relative weight: 1 |
Reflection | Resolution: 1.99→80.19 Å / Num. obs: 120894 / % possible obs: 100 % / Redundancy: 6.5 % / CC1/2: 0.999 / Rmerge(I) obs: 0.066 / Rpim(I) all: 0.028 / Rrim(I) all: 0.071 / Net I/σ(I): 14.1 |
Reflection shell | Resolution: 1.99→2.04 Å / Redundancy: 6.6 % / Rmerge(I) obs: 0.79 / Mean I/σ(I) obs: 2 / Num. unique obs: 8845 / CC1/2: 0.589 / Rpim(I) all: 0.333 / Rrim(I) all: 0.859 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3SL3 Resolution: 1.99→80.19 Å / Cor.coef. Fo:Fc: 0.961 / Cor.coef. Fo:Fc free: 0.932 / SU B: 5.079 / SU ML: 0.134 / Cross valid method: THROUGHOUT / ESU R: 0.169 / ESU R Free: 0.167 / 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 43.247 Å2
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Refinement step | Cycle: 1 / Resolution: 1.99→80.19 Å
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