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Yorodumi- PDB-1y91: Crystal structure of human CDK2 complexed with a pyrazolo[1,5-a]p... -
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-Basic information
Entry | Database: PDB / ID: 1y91 | ||||||
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Title | Crystal structure of human CDK2 complexed with a pyrazolo[1,5-a]pyrimidine inhibitor | ||||||
Components | Cell division protein kinase 2 | ||||||
Keywords | TRANSFERASE / Serine/Threonine protein kinase / CDK2 / ATP-binding / Cell cycle / mitosis / phosphorylation / pyrazolopyrimidine inhibitor | ||||||
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 / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / Activation of ATR in response to replication stress / 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 mitotic cell cycle / regulation of G2/M transition of mitotic cell cycle / cyclin binding / post-translational protein modification / meiotic cell cycle / positive regulation of DNA replication / male germ cell nucleus / response to organic substance / 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 / cell division / protein domain specific binding / protein phosphorylation / DNA repair / protein serine kinase activity / protein serine/threonine kinase activity / centrosome / DNA-templated transcription / positive regulation of cell population proliferation / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / magnesium ion binding / signal transduction / nucleoplasm / ATP binding / nucleus / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.15 Å | ||||||
Authors | Williamson, D.S. / Parratt, M.J. / Torrance, C.J. / Bower, J.F. / Moore, J.D. / Richardson, C.M. / Dokurno, P. / Cansfield, A.D. / Francis, G.L. / Hebdon, R.J. ...Williamson, D.S. / Parratt, M.J. / Torrance, C.J. / Bower, J.F. / Moore, J.D. / Richardson, C.M. / Dokurno, P. / Cansfield, A.D. / Francis, G.L. / Hebdon, R.J. / Howes, R. / Jackson, P.S. / Lockie, A.M. / Murray, J.B. / Nunns, C.L. / Powles, J. / Robertson, A. / Surgenor, A.E. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2005 Title: Structure-guided design of pyrazolo[1,5-a]pyrimidines as inhibitors of human cyclin-dependent kinase 2. Authors: Williamson, D.S. / Parratt, M.J. / Bower, J.F. / Moore, J.D. / Richardson, C.M. / Dokurno, P. / Cansfield, A.D. / Francis, G.L. / Hebdon, R.J. / Howes, R. / Jackson, P.S. / Lockie, A.M. / ...Authors: Williamson, D.S. / Parratt, M.J. / Bower, J.F. / Moore, J.D. / Richardson, C.M. / Dokurno, P. / Cansfield, A.D. / Francis, G.L. / Hebdon, R.J. / Howes, R. / Jackson, P.S. / Lockie, A.M. / Murray, J.B. / Nunns, C.L. / Powles, J. / Robertson, A. / Surgenor, A.E. / Torrance, C.J. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 1y91.cif.gz | 77.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb1y91.ent.gz | 56.6 KB | Display | PDB format |
PDBx/mmJSON format | 1y91.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/y9/1y91 ftp://data.pdbj.org/pub/pdb/validation_reports/y9/1y91 | HTTPS FTP |
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-Related structure data
Related structure data | 1y8yC 1b39S C: citing same article (ref.) 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
#1: Protein | Mass: 33976.488 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CDK2 / Production host: Spodoptera frugiperda (fall armyworm) / Strain (production host): SF21 / References: UniProt: P24941, EC: 2.7.1.37 |
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#2: Chemical | ChemComp-CT9 / |
#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 Å3/Da / Density % sol: 37.8 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7.2 Details: Peg 3350, Hepes, Ammonium acetate, pH 7.2, VAPOR DIFFUSION, HANGING DROP, temperature 293K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU RUH3R / Wavelength: 1.5418 Å |
Detector | Type: RIGAKU RAXIS IV++ / Detector: IMAGE PLATE / Date: Jul 9, 2003 / Details: mirrors |
Radiation | Monochromator: MSC/Osmic Blue / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 1.8→30 Å / Num. all: 24371 / Num. obs: 24371 / % possible obs: 92.9 % / Observed criterion σ(F): 1 / Observed criterion σ(I): 1 / Redundancy: 2.65 % / Biso Wilson estimate: 18.4 Å2 / Rmerge(I) obs: 0.085 / Net I/σ(I): 7.8 |
Reflection shell | Resolution: 1.8→1.86 Å / Redundancy: 1.92 % / Rmerge(I) obs: 0.38 / Mean I/σ(I) obs: 2.2 / Num. unique all: 2575 / % possible all: 64.2 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: pdb entry 1B39 Resolution: 2.15→25 Å / Cor.coef. Fo:Fc: 0.95 / Cor.coef. Fo:Fc free: 0.886 / SU B: 8.389 / SU ML: 0.214 / Cross valid method: THROUGHOUT / σ(F): 1 / ESU R: 0.325 / ESU R Free: 0.271 / 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: 1.4 Å / Solvent model: BABINET MODEL WITH MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 39.164 Å2
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Refinement step | Cycle: LAST / Resolution: 2.15→25 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.15→2.205 Å / Total num. of bins used: 20
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