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Yorodumi- PDB-1pxp: HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR N-[4... -
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-Basic information
Entry | Database: PDB / ID: 1pxp | ||||||
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Title | HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR N-[4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl]-N',N'-dimethyl-benzene-1,4-diamine | ||||||
Components | Cell division protein kinase 2 | ||||||
Keywords | TRANSFERASE / PROTEIN KINASE / CELL CYCLE / PHOSPHORYLATION / CELL DIVISION / MITOSIS / INHIBITION / SERINE/THREONINE-PROTEIN KINASE / ATP-BINDING / 3D-STRUCTURE. | ||||||
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 maintenance in response to DNA damage / G0 and Early G1 / Telomere Extension By Telomerase / cellular response to nitric oxide / Activation of the pre-replicative complex / cyclin-dependent kinase / cyclin-dependent protein serine/threonine kinase activity / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / Regulation of MITF-M-dependent genes involved in cell cycle and proliferation / Cajal body / 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-dependent protein kinase holoenzyme complex / mitotic G1 DNA damage checkpoint signaling / Cyclin A:Cdk2-associated events at S phase entry / condensed chromosome / regulation of mitotic cell cycle / regulation of G2/M transition of mitotic cell cycle / post-translational protein modification / cyclin binding / positive regulation of DNA replication / male germ cell nucleus / meiotic cell cycle / potassium ion transport / DNA Damage/Telomere Stress Induced Senescence / CDK-mediated phosphorylation and removal of Cdc6 / Meiotic recombination / SCF(Skp2)-mediated degradation of p27/p21 / Orc1 removal from chromatin / Transcriptional regulation of granulopoiesis / G1/S transition of mitotic cell cycle / G2/M transition of mitotic cell cycle / Cyclin D associated events in G1 / 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) / peptidyl-serine phosphorylation / regulation of gene expression / Regulation of TP53 Activity through Phosphorylation / transcription regulator complex / Ras protein signal transduction / DNA replication / chromosome, telomeric region / endosome / chromatin remodeling / protein phosphorylation / protein domain specific binding / cell division / protein serine kinase activity / DNA repair / 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 / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.3 Å | ||||||
Authors | Wang, S. / Meades, C. / Wood, G. / Osnowski, A. / Anderson, S. / Yuill, R. / Thomas, M. / Mezna, M. / Jackson, W. / Midgley, C. ...Wang, S. / Meades, C. / Wood, G. / Osnowski, A. / Anderson, S. / Yuill, R. / Thomas, M. / Mezna, M. / Jackson, W. / Midgley, C. / Griffiths, G. / McNae, I. / Wu, S.Y. / McInnes, C. / Zheleva, D. / Walkinshaw, M.D. / Fischer, P.M. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2004 Title: 2-Anilino-4-(thiazol-5-yl)pyrimidine CDK inhibitors: synthesis, SAR analysis, X-ray crystallography, and biological activity. Authors: Wang, S. / Meades, C. / Wood, G. / Osnowski, A. / Anderson, S. / Yuill, R. / Thomas, M. / Mezna, M. / Jackson, W. / Midgley, C. / Griffiths, G. / Fleming, I. / Green, S. / McNae, I. / Wu, S. ...Authors: Wang, S. / Meades, C. / Wood, G. / Osnowski, A. / Anderson, S. / Yuill, R. / Thomas, M. / Mezna, M. / Jackson, W. / Midgley, C. / Griffiths, G. / Fleming, I. / Green, S. / McNae, I. / Wu, S.Y. / McInnes, C. / Zheleva, D. / Walkinshaw, M.D. / Fischer, P.M. #1: Journal: Structure / Year: 2003 Title: Discovery of a novel family of CDK inhibitors with the program LIDAEUS: structural basis for ligand-induced disordering of the activation loop. Authors: Wu, S.Y. / McNae, I. / Kontopidis, G. / McClue, S.J. / McInnes, C. / Stewart, K.J. / Wang, S. / Zheleva, D.I. / Marriage, H. / Lane, D.P. / Taylor, P. / Fischer, P.M. / Walkinshaw, M.D. | ||||||
History |
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Remark 600 | HETEROGEN CK8 500 has alternate conformation with HOH 501,502,503,504,505,506,507,508,and 509. |
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 1pxp.cif.gz | 75.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb1pxp.ent.gz | 55.9 KB | Display | PDB format |
PDBx/mmJSON format | 1pxp.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 1pxp_validation.pdf.gz | 709.6 KB | Display | wwPDB validaton report |
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Full document | 1pxp_full_validation.pdf.gz | 722.1 KB | Display | |
Data in XML | 1pxp_validation.xml.gz | 15.2 KB | Display | |
Data in CIF | 1pxp_validation.cif.gz | 20.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/px/1pxp ftp://data.pdbj.org/pub/pdb/validation_reports/px/1pxp | HTTPS FTP |
-Related structure data
Related structure data | 1pxmC 1pxnC 1pxoC 1hclS 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: 33976.488 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CDK2 / Cell line (production host): Hi5 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: P24941, Transferases; Transferring phosphorus-containing groups; Phosphotransferases with an alcohol group as acceptor |
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#2: Chemical | ChemComp-CK8 / |
#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: 2.01 Å3/Da / Density % sol: 38.84 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7.8 Details: PEG 6000, NA-HEPES, pH 7.8, VAPOR DIFFUSION, HANGING DROP, temperature 277K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: SRS / Beamline: PX9.6 / Wavelength: 0.87 Å |
Detector | Type: ADSC QUANTUM 4 / Detector: CCD |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.87 Å / Relative weight: 1 |
Reflection | Resolution: 2.3→23 Å / Num. obs: 12686 / % possible obs: 98.7 % / Redundancy: 3.4 % / Biso Wilson estimate: 30.5 Å2 / Rmerge(I) obs: 0.5 / Net I/σ(I): 4.9 |
Reflection shell | Resolution: 2.3→2.44 Å / Redundancy: 3.4 % / Rmerge(I) obs: 0.148 / Mean I/σ(I) obs: 4.9 / % possible all: 96.7 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 1HCL Resolution: 2.3→23.6 Å / Rfactor Rfree error: 0.011 / Data cutoff high absF: 1197377.91 / Data cutoff high rms absF: 1197377.91 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 0
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Solvent computation | Solvent model: FLAT MODEL / Bsol: 63.2272 Å2 / ksol: 0.408049 e/Å3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 48.9 Å2
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Refine analyze |
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Refinement step | Cycle: LAST / Resolution: 2.3→23.6 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.3→2.44 Å / Rfactor Rfree error: 0.029 / Total num. of bins used: 6
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Xplor file |
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