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Yorodumi- PDB-4uwg: Discovery of (2S)-8-((3R)-3-Methylmorpholin-4-yl)-1-(3-methyl-2-o... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4uwg | ||||||
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Title | Discovery of (2S)-8-((3R)-3-Methylmorpholin-4-yl)-1-(3-methyl-2-oxo- butyl)-2-(trifluoromethyl)-3,4-dihydro-2H-pyrimido(1,2-a)pyrimidin-6- one: a Novel Potent and Selective Inhibitor of Vps34 for the Treatment of Solid Tumors | ||||||
Components | PHOSPHATIDYLINOSITOL 3-KINASE CATALYTIC SUBUNIT TYPE 3 | ||||||
Keywords | TRANSFERASE | ||||||
Function / homology | Function and homology information Toll Like Receptor 9 (TLR9) Cascade / protein lipidation / Synthesis of PIPs at the late endosome membrane / phosphatidylinositol 3-kinase complex, class III / Synthesis of PIPs at the early endosome membrane / phosphatidylinositol 3-kinase complex, class III, type II / phosphatidylinositol 3-kinase complex, class III, type I / positive regulation by host of viral genome replication / Synthesis of PIPs at the Golgi membrane / phosphatidylinositol kinase activity ...Toll Like Receptor 9 (TLR9) Cascade / protein lipidation / Synthesis of PIPs at the late endosome membrane / phosphatidylinositol 3-kinase complex, class III / Synthesis of PIPs at the early endosome membrane / phosphatidylinositol 3-kinase complex, class III, type II / phosphatidylinositol 3-kinase complex, class III, type I / positive regulation by host of viral genome replication / Synthesis of PIPs at the Golgi membrane / phosphatidylinositol kinase activity / protein localization to phagophore assembly site / protein targeting to lysosome / early endosome to late endosome transport / phosphatidylinositol-mediated signaling / phagophore assembly site / Translation of Replicase and Assembly of the Replication Transcription Complex / autolysosome / phosphatidylinositol 3-kinase / phosphatidylinositol-3-phosphate biosynthetic process / Macroautophagy / 1-phosphatidylinositol-3-kinase activity / axoneme / autophagosome maturation / phosphatidylinositol phosphate biosynthetic process / autophagosome assembly / PI3K Cascade / RHO GTPases Activate NADPH Oxidases / regulation of macroautophagy / cellular response to glucose starvation / regulation of cytokinesis / regulation of autophagy / macroautophagy / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / autophagy / peroxisome / endocytosis / phagocytic vesicle membrane / late endosome / Translation of Replicase and Assembly of the Replication Transcription Complex / kinase activity / midbody / endosome / protein kinase activity / cell cycle / cell division / phosphorylation / SARS-CoV-2 activates/modulates innate and adaptive immune responses / ATP binding / membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | HOMO SAPIENS (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.7 Å | ||||||
Authors | Pasquier, B. / El-Ahmad, Y. / Filoche-Romme, B. / Dureuil, C. / Fassy, F. / Abecassis, P.Y. / Mathieu, M. / Bertrand, T. / Benard, T. / Barriere, C. ...Pasquier, B. / El-Ahmad, Y. / Filoche-Romme, B. / Dureuil, C. / Fassy, F. / Abecassis, P.Y. / Mathieu, M. / Bertrand, T. / Benard, T. / Barriere, C. / ElBatti, S. / Letallec, J.P. / Sonnefraud, V. / Brollo, M. / Delbarre, L. / Loyau, V. / Pilorge, F. / Bertin, L. / Richepin, P. / Arigon, J. / Labrosse, J.R. / Clement, J. / Durand, F. / Combet, R. / Perraut, P. / Leroy, V. / Gay, F. / Lefrancois, D. / Bretin, F. / Marquette, J.P. / Michot, N. / Caron, A. / Castell, C. / Schio, L. / McCort, G. / Goulaouic, H. / Garcia-Echeverria, C. / Ronan, B. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2015 Title: Discovery of (2S)-8-[(3R)-3-Methylmorpholin-4-Yl]-1-(3-Methyl-2-Oxobutyl)-2-(Trifluoromethyl)-3,4-Dihydro-2H-Pyrimido[1,2-A]Pyrimidin-6-One: A Novel Potent and Selective Inhibitor of Vps34 for ...Title: Discovery of (2S)-8-[(3R)-3-Methylmorpholin-4-Yl]-1-(3-Methyl-2-Oxobutyl)-2-(Trifluoromethyl)-3,4-Dihydro-2H-Pyrimido[1,2-A]Pyrimidin-6-One: A Novel Potent and Selective Inhibitor of Vps34 for the Treatment of Solid Tumors. Authors: Pasquier, B. / El-Ahmad, Y. / Filoche-Romme, B. / Dureuil, C. / Fassy, F. / Abecassis, P. / Mathieu, M. / Bertrand, T. / Benard, T. / Barriere, C. / El Batti, S. / Letallec, J. / Sonnefraud, ...Authors: Pasquier, B. / El-Ahmad, Y. / Filoche-Romme, B. / Dureuil, C. / Fassy, F. / Abecassis, P. / Mathieu, M. / Bertrand, T. / Benard, T. / Barriere, C. / El Batti, S. / Letallec, J. / Sonnefraud, V. / Brollo, M. / Delbarre, L. / Loyau, V. / Pilorge, F. / Bertin, L. / Richepin, P. / Arigon, J. / Labrosse, J. / Clement, J. / Durand, F. / Combet, R. / Perraut, P. / Leroy, V. / Gay, F. / Lefrancois, D. / Bretin, F. / Marquette, J. / Michot, N. / Caron, A. / Castell, C. / Schio, L. / Mccort, G. / Goulaouic, H. / Garcia-Echeverria, C. / Ronan, B. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4uwg.cif.gz | 125.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4uwg.ent.gz | 95.6 KB | Display | PDB format |
PDBx/mmJSON format | 4uwg.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/uw/4uwg ftp://data.pdbj.org/pub/pdb/validation_reports/uw/4uwg | HTTPS FTP |
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-Related structure data
Related structure data | 4uwfSC 4uwhC 4uwkC 4uwlC 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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Unit cell |
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-Components
#1: Protein | Mass: 68597.391 Da / Num. of mol.: 1 Fragment: VPS34 HELICAL AND KINASE DOMAINS, RESIDUES 282-879 Source method: isolated from a genetically manipulated source Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PET / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: Q8NEB9, phosphatidylinositol 3-kinase | ||||
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#2: Chemical | #3: Chemical | ChemComp-RBQ / ( | #4: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.41 Å3/Da / Density % sol: 63.9 % / Description: NONE |
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Crystal grow | pH: 8.5 / Details: AMMONIUM SULFATE 2M - TRIS 100MM PH 8.5 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: SOLEIL / Beamline: PROXIMA 1 / Wavelength: 0.98011 |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Jul 12, 2013 / Details: KIRKPATRICK-BAEZ PAIR OF BI-MORPH MIRRORS |
Radiation | Monochromator: SI (111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.98011 Å / Relative weight: 1 |
Reflection | Resolution: 2.7→49 Å / Num. obs: 24128 / % possible obs: 99.2 % / Observed criterion σ(I): 3 / Redundancy: 6.4 % / Biso Wilson estimate: 63.61 Å2 / Rmerge(I) obs: 0.09 / Net I/σ(I): 14.2 |
Reflection shell | Resolution: 2.7→2.83 Å / Redundancy: 6.1 % / Rmerge(I) obs: 0.63 / Mean I/σ(I) obs: 2.5 / % possible all: 92.9 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 4UWF Resolution: 2.7→46.88 Å / Cor.coef. Fo:Fc: 0.9132 / Cor.coef. Fo:Fc free: 0.8941 / SU R Cruickshank DPI: 0.42 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.422 / SU Rfree Blow DPI: 0.255 / SU Rfree Cruickshank DPI: 0.258
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Displacement parameters | Biso mean: 62.47 Å2
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Refine analyze | Luzzati coordinate error obs: 0.332 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.7→46.88 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.7→2.82 Å / Total num. of bins used: 12
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