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Yorodumi- PDB-7xaa: Crystal structure of PDE4D catalytic domain complexed with compou... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7xaa | ||||||||||||
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Title | Crystal structure of PDE4D catalytic domain complexed with compound 21d | ||||||||||||
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 / 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 / MOLECULAR REPLACEMENT / Resolution: 2.10041402486 Å | ||||||||||||
Authors | Huang, Y.-Y. / He, X. / Luo, H.-B. | ||||||||||||
Funding support | China, 3items
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Citation | Journal: Eur.J.Med.Chem. / Year: 2022 Title: Discovery of novel PDE4 inhibitors targeting the M-pocket from natural mangostanin with improved safety for the treatment of Inflammatory Bowel Diseases. Authors: Liu, H. / Wang, Q. / Huang, Y. / Deng, J. / Xie, X. / Zhu, J. / Yuan, Y. / He, Y.M. / Huang, Y.Y. / Luo, H.B. / He, X. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7xaa.cif.gz | 196.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7xaa.ent.gz | 123.3 KB | Display | PDB format |
PDBx/mmJSON format | 7xaa.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xa/7xaa ftp://data.pdbj.org/pub/pdb/validation_reports/xa/7xaa | HTTPS FTP |
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-Related structure data
Related structure data | 7xabC 5wqaS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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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 grow | Temperature: 277 K / Method: vapor diffusion, hanging drop Details: 0.1 M HEPES (pH 7.4), 0.1 M MgCl2, 15% PEG 3350, 10% isopropanol, 25% ethylene glycol |
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-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: Oct 25, 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→22.4211 Å / Num. obs: 45632 / % possible obs: 99.8 % / Redundancy: 4.1 % / Rmerge(I) obs: 0.056 / Net I/σ(I): 19.4 |
Reflection shell | Resolution: 2.1→2.2 Å / Redundancy: 3.3 % / Rmerge(I) obs: 0.223 / Mean I/σ(I) obs: 4.8 / Num. unique obs: 4484 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5WQA Resolution: 2.10041402486→22.4210196093 Å / SU ML: 0.207802466977 / Cross valid method: NONE / σ(F): 1.36947700738 / Phase error: 21.5140155101 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: 23.4695763302 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.10041402486→22.4210196093 Å
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Refine LS restraints |
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LS refinement shell |
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