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Yorodumi- PDB-5lbo: Crystal structure of human phosphodiesterase 4D2 catalytic domain... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5lbo | ||||||
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Title | Crystal structure of human phosphodiesterase 4D2 catalytic domain with inhibitor NPD-001 | ||||||
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 / positive regulation of heart rate / adrenergic receptor signaling pathway / heterocyclic compound binding / regulation of cell communication by electrical coupling involved in cardiac conduction / cAMP catabolic process / negative regulation of peptidyl-serine phosphorylation / 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 / calcium channel complex / cellular response to epinephrine stimulus / positive regulation of interleukin-2 production / cAMP-mediated signaling / 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: 2.25 Å | ||||||
Authors | Singh, A.K. / Brown, D.G. | ||||||
Citation | Journal: J. Med. Chem. / Year: 2018 Title: Targeting a Subpocket in Trypanosoma brucei Phosphodiesterase B1 (TbrPDEB1) Enables the Structure-Based Discovery of Selective Inhibitors with Trypanocidal Activity. Authors: Blaazer, A.R. / Singh, A.K. / de Heuvel, E. / Edink, E. / Orrling, K.M. / Veerman, J.J.N. / van den Bergh, T. / Jansen, C. / Balasubramaniam, E. / Mooij, W.J. / Custers, H. / Sijm, M. / ...Authors: Blaazer, A.R. / Singh, A.K. / de Heuvel, E. / Edink, E. / Orrling, K.M. / Veerman, J.J.N. / van den Bergh, T. / Jansen, C. / Balasubramaniam, E. / Mooij, W.J. / Custers, H. / Sijm, M. / Tagoe, D.N.A. / Kalejaiye, T.D. / Munday, J.C. / Tenor, H. / Matheeussen, A. / Wijtmans, M. / Siderius, M. / de Graaf, C. / Maes, L. / de Koning, H.P. / Bailey, D.S. / Sterk, G.J. / 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 | 5lbo.cif.gz | 299.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5lbo.ent.gz | 240.5 KB | Display | PDB format |
PDBx/mmJSON format | 5lbo.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5lbo_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 5lbo_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 5lbo_validation.xml.gz | 54.4 KB | Display | |
Data in CIF | 5lbo_validation.cif.gz | 76.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/lb/5lbo ftp://data.pdbj.org/pub/pdb/validation_reports/lb/5lbo | HTTPS FTP |
-Related structure data
Related structure data | 5g2bC 5g57C 5g5vC 5l8cC 5l8yC 5l9hC 5laqC 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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4 |
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Component-ID: _ / End auth comp-ID: ILE / End label comp-ID: ILE / Refine code: _
NCS ensembles :
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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: UNP 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, 600 molecules
#2: Chemical | ChemComp-ZN / #3: Chemical | ChemComp-MG / #4: Chemical | ChemComp-EDO / #5: Chemical | #6: Chemical | ChemComp-6M5 / ( #7: Chemical | #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: 2.63 Å3/Da / Density % sol: 53.19 % |
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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 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.97623 Å |
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Apr 28, 2016 / Details: CRL |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97623 Å / Relative weight: 1 |
Reflection | Resolution: 2.25→160.8 Å / Num. obs: 80611 / % possible obs: 96.4 % / Redundancy: 6.5 % / CC1/2: 0.998 / Rmerge(I) obs: 0.113 / Net I/σ(I): 13.8 |
Reflection shell | Resolution: 2.25→2.38 Å / Redundancy: 6.5 % / Rmerge(I) obs: 0.763 / Mean I/σ(I) obs: 2.6 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3SL3 Resolution: 2.25→91.4 Å / Cor.coef. Fo:Fc: 0.961 / Cor.coef. Fo:Fc free: 0.942 / SU B: 5.815 / SU ML: 0.137 / Cross valid method: THROUGHOUT / ESU R: 0.247 / ESU R Free: 0.189 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 mean: 45.341 Å2
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Refinement step | Cycle: 1 / Resolution: 2.25→91.4 Å
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Refine LS restraints |
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