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Yorodumi- PDB-7f2l: Crystal structure of PDE4D catalytic domain complexed with compou... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7f2l | ||||||||||||
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Title | Crystal structure of PDE4D catalytic domain complexed with compound 18a | ||||||||||||
Components | Isoform 3 of cAMP-specific 3',5'-cyclic phosphodiesterase 4D | ||||||||||||
Keywords | HYDROLASE / PDE4 inhibitor | ||||||||||||
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 / 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 relaxation of cardiac muscle / negative regulation of heart contraction / 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 / calcium channel regulator activity / 3',5'-cyclic-GMP phosphodiesterase activity / 3',5'-cyclic-AMP phosphodiesterase activity / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / cAMP binding / cellular response to cAMP / calcium channel complex / cellular response to epinephrine stimulus / positive regulation of interleukin-2 production / regulation of heart rate / cAMP-mediated signaling / 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 / membrane / nucleus / metal ion binding / plasma membrane / cytosol Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | X-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.10111436093 Å | ||||||||||||
Authors | Huang, Y.-Y. / He, X. / Luo, H.-B. | ||||||||||||
Funding support | China, 3items
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Citation | Journal: J.Med.Chem. / Year: 2021 Title: Mangostanin Derivatives as Novel and Orally Active Phosphodiesterase 4 Inhibitors for the Treatment of Idiopathic Pulmonary Fibrosis with Improved Safety. Authors: Huang, Y.Y. / Deng, J. / Tian, Y.J. / Liang, J. / Xie, X. / Huang, Y. / Zhu, J. / Zhu, Z. / Zhou, Q. / He, X. / Luo, H.B. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7f2l.cif.gz | 161.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7f2l.ent.gz | 121.1 KB | Display | PDB format |
PDBx/mmJSON format | 7f2l.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/f2/7f2l ftp://data.pdbj.org/pub/pdb/validation_reports/f2/7f2l | HTTPS FTP |
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-Related structure data
Related structure data | 7f2kC 7f2mC 5wqaS S: Starting model for refinement C: citing same article (ref.) |
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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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Unit cell |
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-Components
#1: Protein | Mass: 57859.504 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PDE4D, DPDE3 / Production host: Escherichia coli BL21 (bacteria) References: UniProt: Q08499, 3',5'-cyclic-AMP phosphodiesterase #2: Chemical | #3: Chemical | #4: Chemical | #5: Water | ChemComp-HOH / | Has ligand of interest | Y | |
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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: 1.65 Å3/Da / Density % sol: 25.44 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop Details: 0.1 M HEPES (pH 7.4), 0.1 M MgCl2, 15% PEG3350, 10% isopropanol, and 25% ethylene glycol |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU / Wavelength: 1.5418 Å |
Detector | Type: RIGAKU HyPix-3000 / Detector: PIXEL / Date: Feb 22, 2021 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 2.1→23.525 Å / Num. obs: 45324 / % possible obs: 99.5 % / Redundancy: 3.9 % / Biso Wilson estimate: 18.8532110554 Å2 / Rmerge(I) obs: 0.09 / Net I/σ(I): 13.7 |
Reflection shell | Resolution: 2.1→2.2 Å / Redundancy: 2.5 % / Rmerge(I) obs: 0.411 / Mean I/σ(I) obs: 2.4 / Num. unique obs: 4387 / % possible all: 97.8 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5WQA Resolution: 2.10111436093→23.5247305334 Å / SU ML: 0.242109487645 / Cross valid method: NONE / σ(F): 1.3569409462 / Phase error: 23.6438362324 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 23.4953769912 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.10111436093→23.5247305334 Å
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Refine LS restraints |
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LS refinement shell |
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