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Yorodumi- PDB-6oqi: CDK2 in complex with Cpd14 (5-fluoro-4-(4-methyl-5,6,7,8-tetrahyd... -
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-Basic information
Entry | Database: PDB / ID: 6oqi | ||||||
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Title | CDK2 in complex with Cpd14 (5-fluoro-4-(4-methyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a]azepin-3-yl)-N-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)pyrimidin-2-amine) | ||||||
Components | Cyclin-dependent kinase 2 | ||||||
Keywords | TRANSFERASE/TRANSFERASE inhibitor / kinase / TRANSFERASE / TRANSFERASE-TRANSFERASE inhibitor complex | ||||||
Function / homology | Function and homology information cyclin A1-CDK2 complex / cyclin E2-CDK2 complex / cyclin E1-CDK2 complex / cyclin A2-CDK2 complex / positive regulation of DNA-templated DNA replication initiation / G2 Phase / cyclin-dependent protein kinase activity / Y chromosome / Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes / positive regulation of heterochromatin formation ...cyclin A1-CDK2 complex / cyclin E2-CDK2 complex / cyclin E1-CDK2 complex / cyclin A2-CDK2 complex / positive regulation of DNA-templated DNA replication initiation / G2 Phase / cyclin-dependent protein kinase activity / Y chromosome / Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes / positive regulation of heterochromatin formation / p53-Dependent G1 DNA Damage Response / X chromosome / PTK6 Regulates Cell Cycle / regulation of anaphase-promoting complex-dependent catabolic process / Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) / centriole replication / Regulation of APC/C activators between G1/S and early anaphase / centrosome duplication / Telomere Extension By Telomerase / G0 and Early G1 / Activation of the pre-replicative complex / cyclin-dependent protein kinase holoenzyme complex / cellular response to nitric oxide / Cajal body / cyclin-dependent kinase / cyclin-dependent protein serine/threonine kinase activity / Activation of ATR in response to replication stress / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / Cyclin E associated events during G1/S transition / Cyclin A/B1/B2 associated events during G2/M transition / Cyclin A:Cdk2-associated events at S phase entry / condensed chromosome / mitotic G1 DNA damage checkpoint signaling / regulation of G2/M transition of mitotic cell cycle / post-translational protein modification / response to organic substance / meiotic cell cycle / male germ cell nucleus / cyclin binding / G1/S transition of mitotic cell cycle / potassium ion transport / DNA Damage/Telomere Stress Induced Senescence / CDK-mediated phosphorylation and removal of Cdc6 / SCF(Skp2)-mediated degradation of p27/p21 / Meiotic recombination / Orc1 removal from chromatin / Transcriptional regulation of granulopoiesis / Cyclin D associated events in G1 / G2/M transition of mitotic cell cycle / cellular senescence / Regulation of TP53 Degradation / nuclear envelope / Factors involved in megakaryocyte development and platelet production / Processing of DNA double-strand break ends / Senescence-Associated Secretory Phenotype (SASP) / regulation of gene expression / peptidyl-serine phosphorylation / Ras protein signal transduction / Regulation of TP53 Activity through Phosphorylation / transcription regulator complex / DNA replication / chromosome, telomeric region / endosome / chromatin remodeling / protein domain specific binding / cell division / protein phosphorylation / DNA repair / protein serine kinase activity / protein serine/threonine kinase activity / DNA-templated transcription / centrosome / positive regulation of cell population proliferation / positive regulation of DNA-templated transcription / magnesium ion binding / negative regulation of transcription by RNA polymerase II / signal transduction / nucleoplasm / ATP binding / nucleus / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2 Å | ||||||
Authors | Murray, J.M. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2019 Title: Design of a brain-penetrant CDK4/6 inhibitor for glioblastoma. Authors: Bronner, S.M. / Merrick, K.A. / Murray, J. / Salphati, L. / Moffat, J.G. / Pang, J. / Sneeringer, C.J. / Dompe, N. / Cyr, P. / Purkey, H. / Boenig, G.L. / Li, J. / Kolesnikov, A. / Larouche- ...Authors: Bronner, S.M. / Merrick, K.A. / Murray, J. / Salphati, L. / Moffat, J.G. / Pang, J. / Sneeringer, C.J. / Dompe, N. / Cyr, P. / Purkey, H. / Boenig, G.L. / Li, J. / Kolesnikov, A. / Larouche-Gauthier, R. / Lai, K.W. / Shen, X. / Aubert-Nicol, S. / Chen, Y.C. / Cheong, J. / Crawford, J.J. / Hafner, M. / Haghshenas, P. / Jakalian, A. / Leclerc, J.P. / Lim, N.K. / O'Brien, T. / Plise, E.G. / Shalan, H. / Sturino, C. / Wai, J. / Xiao, Y. / Yin, J. / Zhao, L. / Gould, S. / Olivero, A. / Heffron, T.P. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6oqi.cif.gz | 137.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6oqi.ent.gz | 104.8 KB | Display | PDB format |
PDBx/mmJSON format | 6oqi.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/oq/6oqi ftp://data.pdbj.org/pub/pdb/validation_reports/oq/6oqi | HTTPS FTP |
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-Related structure data
Related structure data | 6oqlC 6oqoC 1aqaS 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: 34123.660 Da / Num. of mol.: 1 / Fragment: kinase domain Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CDK2, CDKN2 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P24941, cyclin-dependent kinase |
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#2: Chemical | ChemComp-N14 / |
#3: 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: 2.03 Å3/Da / Density % sol: 39.45 % |
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Crystal grow | Temperature: 292 K / Method: evaporation / pH: 7.5 Details: 10-12% PEG 4K, 50 mM Hepes pH7.5, 50 mM Ammonia Acetate |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | ||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 0.999 Å | ||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS3 S 6M / Detector: PIXEL / Date: Feb 28, 2018 | ||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.999 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||
Reflection | Resolution: 1.858→42.941 Å / Num. obs: 23997 / % possible obs: 100 % / Redundancy: 12.7 % / Biso Wilson estimate: 35.72 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.12 / Rpim(I) all: 0.035 / Rrim(I) all: 0.125 / Net I/σ(I): 13.4 / Num. measured all: 305459 | ||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1AQA Resolution: 2→42.941 Å / SU ML: 0.31 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 28.06
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 177.65 Å2 / Biso mean: 53.7083 Å2 / Biso min: 19.29 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2→42.941 Å
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 7 / % reflection obs: 100 %
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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