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Yorodumi- PDB-6njj: Crystal Structure of the PDE4D Catalytic Domain and UCR2 Regulato... -
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-Basic information
Entry | Database: PDB / ID: 6njj | ||||||
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Title | Crystal Structure of the PDE4D Catalytic Domain and UCR2 Regulatory Helix with BPN14770 | ||||||
Components | cAMP-specific 3',5'-cyclic phosphodiesterase 4D | ||||||
Keywords | HYDROLASE/HYDROLASE INHIBITOR / PDE4D / CAMP-SPECIFIC 3'5'-CYCLIC PHOSPHODIESTERASE 4D / UCR2 / cAMP / HYDROLASE / HYDROLASE-HYDROLASE INHIBITOR complex | ||||||
Function / homology | Function and homology information signaling receptor regulator activity / negative regulation of relaxation of cardiac muscle / negative regulation of heart contraction / 3',5'-cyclic-AMP phosphodiesterase / positive regulation of interleukin-5 production / regulation of cardiac muscle cell contraction / establishment of endothelial barrier / negative regulation of cAMP-mediated signaling / beta-2 adrenergic receptor binding / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel ...signaling receptor regulator activity / negative regulation of relaxation of cardiac muscle / negative regulation of heart contraction / 3',5'-cyclic-AMP phosphodiesterase / positive regulation of interleukin-5 production / regulation of cardiac muscle cell contraction / establishment of endothelial barrier / negative regulation of cAMP-mediated signaling / beta-2 adrenergic receptor binding / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / positive regulation of heart rate / heterocyclic compound binding / adrenergic receptor signaling pathway / voltage-gated calcium channel complex / regulation of cell communication by electrical coupling involved in cardiac conduction / cAMP catabolic process / calcium channel regulator activity / cAMP-mediated signaling / 3',5'-cyclic-nucleotide phosphodiesterase activity / 3',5'-cyclic-AMP phosphodiesterase activity / DARPP-32 events / negative regulation of peptidyl-serine phosphorylation / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / cAMP binding / cellular response to cAMP / cellular response to epinephrine stimulus / calcium channel complex / positive regulation of interleukin-2 production / regulation of heart rate / positive regulation of type II interferon production / ATPase binding / T cell receptor signaling pathway / G alpha (s) signalling events / scaffold protein binding / transmembrane transporter binding / apical plasma membrane / centrosome / perinuclear region of cytoplasm / enzyme binding / signal transduction / membrane / metal ion binding / nucleus / plasma membrane / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.3 Å | ||||||
Authors | Fox III, D. / Fairman, J.W. / Gurney, M.E. | ||||||
Funding support | United States, 1items
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Citation | Journal: J.Med.Chem. / Year: 2019 Title: Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders. Authors: Gurney, M.E. / Nugent, R.A. / Mo, X. / Sindac, J.A. / Hagen, T.J. / Fox 3rd, D. / O'Donnell, J.M. / Zhang, C. / Xu, Y. / Zhang, H.T. / Groppi, V.E. / Bailie, M. / White, R.E. / Romero, D.L. ...Authors: Gurney, M.E. / Nugent, R.A. / Mo, X. / Sindac, J.A. / Hagen, T.J. / Fox 3rd, D. / O'Donnell, J.M. / Zhang, C. / Xu, Y. / Zhang, H.T. / Groppi, V.E. / Bailie, M. / White, R.E. / Romero, D.L. / Vellekoop, A.S. / Walker, J.R. / Surman, M.D. / Zhu, L. / Campbell, R.F. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6njj.cif.gz | 293.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6njj.ent.gz | 232.9 KB | Display | PDB format |
PDBx/mmJSON format | 6njj.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/nj/6njj ftp://data.pdbj.org/pub/pdb/validation_reports/nj/6njj | HTTPS FTP |
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-Related 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: 42593.051 Da / Num. of mol.: 4 / Mutation: S579A, S581A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PDE4D, DPDE3 / Plasmid: PEMB44 / Production host: Trichoplusia ni (cabbage looper) References: UniProt: Q08499, 3',5'-cyclic-AMP phosphodiesterase |
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-Non-polymers , 7 types, 526 molecules
#2: Chemical | ChemComp-ZN / #3: Chemical | ChemComp-MG / #4: Chemical | ChemComp-KR7 / ( #5: Chemical | #6: Chemical | ChemComp-SO4 / #7: Chemical | ChemComp-EDO / | #8: 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: 2.14 Å3/Da / Density % sol: 42.65 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, sitting drop / pH: 6.3 Details: 8.8MG/ML VCID7620 + 0.5MM BPN- 014770 (EBSI4045) IN A PROTEIN SOLUTION CONTAINING 10MM HEPES PH 7.5, 100MM NACL, 1MM DTT, 0.1MM ZNCL2, 0.1MM MGCL2 (BATCH 1214057) AGAINST OPTIMIZATION SCREEN ...Details: 8.8MG/ML VCID7620 + 0.5MM BPN- 014770 (EBSI4045) IN A PROTEIN SOLUTION CONTAINING 10MM HEPES PH 7.5, 100MM NACL, 1MM DTT, 0.1MM ZNCL2, 0.1MM MGCL2 (BATCH 1214057) AGAINST OPTIMIZATION SCREEN TET_MPC8_JCH7 (OPT SCREEN BASED ON MORPHEUS C8 AND JCSG H7); 6.25% W/V PEG1,000, 20.91% W/V PEG3350, 6.25% W/V MPD, 0.2M AMMONIUM SULFATE, 0.1MM BIS- TRIS PH 6.3, CRYO-PROTECTED - 20% ETHYLENE GLYCOL, CRYSTAL TRACKING ID 247599D11 (WEV9-9), PH 6.30, VAPOR DIFFUSION, SITTING DROP, TEMPERATURE 289K PH range: 6.3 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.3 / Wavelength: 0.9765 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Sep 22, 2013 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9765 Å / Relative weight: 1 |
Reflection | Resolution: 2.3→50 Å / Num. obs: 64038 / % possible obs: 99.7 % / Observed criterion σ(I): -3 / Redundancy: 3.8 % / Biso Wilson estimate: 39.87 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.086 / Net I/σ(I): 13.68 |
Reflection shell | Resolution: 2.3→2.36 Å / Redundancy: 3.8 % / Rmerge(I) obs: 0.558 / Mean I/σ(I) obs: 2.6 / Num. unique obs: 4710 / CC1/2: 0.859 / % possible all: 99.8 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.3→45.49 Å / Cor.coef. Fo:Fc: 0.964 / Cor.coef. Fo:Fc free: 0.94 / SU B: 7.129 / SU ML: 0.166 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.333 / ESU R Free: 0.216 / Details: HYDROGENS HAVE BEEN ADDED IN THE
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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: 31.06 Å2
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Refinement step | Cycle: LAST / Resolution: 2.3→45.49 Å
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Refine LS restraints |
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