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Yorodumi- PDB-5mhp: Novel Imidazo[1,2-a]pyridine Derivatives with Potent Autotaxin/EN... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5mhp | |||||||||
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Title | Novel Imidazo[1,2-a]pyridine Derivatives with Potent Autotaxin/ENPP2 Inhibitor Activity | |||||||||
Components | Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 | |||||||||
Keywords | HYDROLASE / ATX / Inhibitor / ENPP2 | |||||||||
Function / homology | Function and homology information Vitamin B5 (pantothenate) metabolism / alkylglycerophosphoethanolamine phosphodiesterase / sphingolipid catabolic process / phospholipid catabolic process / phosphatidylcholine catabolic process / positive regulation of lamellipodium morphogenesis / lysophospholipase activity / phosphodiesterase I activity / scavenger receptor activity / alkylglycerophosphoethanolamine phosphodiesterase activity ...Vitamin B5 (pantothenate) metabolism / alkylglycerophosphoethanolamine phosphodiesterase / sphingolipid catabolic process / phospholipid catabolic process / phosphatidylcholine catabolic process / positive regulation of lamellipodium morphogenesis / lysophospholipase activity / phosphodiesterase I activity / scavenger receptor activity / alkylglycerophosphoethanolamine phosphodiesterase activity / polysaccharide binding / positive regulation of epithelial cell migration / estrous cycle / regulation of cell migration / cell motility / chemotaxis / positive regulation of peptidyl-tyrosine phosphorylation / nucleic acid binding / hydrolase activity / immune response / calcium ion binding / extracellular space / zinc ion binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.43 Å | |||||||||
Authors | Fleury, D. / Mueller, I. / Lamers, M. / Triballeau, N. / Mollat, P. / Vercheval, L. | |||||||||
Citation | Journal: J. Med. Chem. / Year: 2017 Title: Discovery of 2-[[2-Ethyl-6-[4-[2-(3-hydroxyazetidin-1-yl)-2-oxoethyl]piperazin-1-yl]-8-methylimidazo[1,2-a]pyridin-3-yl]methylamino]-4-(4-fluorophenyl)thiazole-5-carbonitrile (GLPG1690), a ...Title: Discovery of 2-[[2-Ethyl-6-[4-[2-(3-hydroxyazetidin-1-yl)-2-oxoethyl]piperazin-1-yl]-8-methylimidazo[1,2-a]pyridin-3-yl]methylamino]-4-(4-fluorophenyl)thiazole-5-carbonitrile (GLPG1690), a First-in-Class Autotaxin Inhibitor Undergoing Clinical Evaluation for the Treatment of Idiopathic Pulmonary Fibrosis. Authors: Desroy, N. / Housseman, C. / Bock, X. / Joncour, A. / Bienvenu, N. / Cherel, L. / Labeguere, V. / Rondet, E. / Peixoto, C. / Grassot, J.M. / Picolet, O. / Annoot, D. / Triballeau, N. / ...Authors: Desroy, N. / Housseman, C. / Bock, X. / Joncour, A. / Bienvenu, N. / Cherel, L. / Labeguere, V. / Rondet, E. / Peixoto, C. / Grassot, J.M. / Picolet, O. / Annoot, D. / Triballeau, N. / Monjardet, A. / Wakselman, E. / Roncoroni, V. / Le Tallec, S. / Blanque, R. / Cottereaux, C. / Vandervoort, N. / Christophe, T. / Mollat, P. / Lamers, M. / Auberval, M. / Hrvacic, B. / Ralic, J. / Oste, L. / van der Aar, E. / Brys, R. / Heckmann, B. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5mhp.cif.gz | 179.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5mhp.ent.gz | 135.9 KB | Display | PDB format |
PDBx/mmJSON format | 5mhp.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5mhp_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 5mhp_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 5mhp_validation.xml.gz | 28.6 KB | Display | |
Data in CIF | 5mhp_validation.cif.gz | 41.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/mh/5mhp ftp://data.pdbj.org/pub/pdb/validation_reports/mh/5mhp | HTTPS FTP |
-Related structure data
Related structure data | 5m7mS 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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Unit cell |
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-Components
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 100123.742 Da / Num. of mol.: 1 / Mutation: S493P Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ENPP2, ATX, PDNP2 / Plasmid: pTT5 / Cell line (production host): HEK293 / Organ (production host): kidney / Production host: Homo sapiens (human) / Tissue (production host): embryonic References: UniProt: Q13822, alkylglycerophosphoethanolamine phosphodiesterase |
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-Sugars , 2 types, 2 molecules
#2: Polysaccharide | alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D- ...alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
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#3: Sugar | ChemComp-NAG / |
-Non-polymers , 9 types, 172 molecules
#4: Chemical | #5: Chemical | ChemComp-CA / | #6: Chemical | ChemComp-MG / | #7: Chemical | ChemComp-IOD / | #8: Chemical | #9: Chemical | ChemComp-SCN / | #10: Chemical | #11: Chemical | ChemComp-7NB / | #12: 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: 2.4 Å3/Da / Density % sol: 48.81 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop Details: PEG 3350 15%, thiocyanate 0.4 M and ammonium iodide 0.1 M |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I02 / Wavelength: 0.9795 Å |
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Jul 12, 2013 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9795 Å / Relative weight: 1 |
Reflection | Resolution: 2.43→79.53 Å / Num. obs: 35498 / % possible obs: 98.8 % / Redundancy: 3.3 % / Rmerge(I) obs: 0.075 / Net I/σ(I): 10.5 |
Reflection shell | Resolution: 2.43→2.49 Å / Redundancy: 3 % / Rmerge(I) obs: 0.56 / Mean I/σ(I) obs: 1.9 / % possible all: 96.9 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5M7M Resolution: 2.43→75.87 Å / Cor.coef. Fo:Fc: 0.937 / Cor.coef. Fo:Fc free: 0.912 / SU B: 9.296 / SU ML: 0.204 / Cross valid method: THROUGHOUT / ESU R: 0.454 / ESU R Free: 0.265 / Stereochemistry target values: MAXIMUM LIKELIHOOD / 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 / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 41.347 Å2
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Refinement step | Cycle: 1 / Resolution: 2.43→75.87 Å
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