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Yorodumi- PDB-8h6t: Complex structure of CDK2/Cyclin E1 and a potent, selective small... -
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-Basic information
Entry | Database: PDB / ID: 8h6t | ||||||
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Title | Complex structure of CDK2/Cyclin E1 and a potent, selective small molecule inhibitor | ||||||
Components |
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Keywords | CELL CYCLE / Inhibitor / Complex / Selective / Anti-tumor | ||||||
Function / homology | Function and homology information positive regulation of mesenchymal stem cell proliferation / homologous chromosome pairing at meiosis / RHOBTB3 ATPase cycle / cyclin-dependent protein serine/threonine kinase regulator activity / G1/S-Specific Transcription / cyclin A1-CDK2 complex / cyclin E2-CDK2 complex / cyclin E1-CDK2 complex / cyclin A2-CDK2 complex / positive regulation of DNA-templated DNA replication initiation ...positive regulation of mesenchymal stem cell proliferation / homologous chromosome pairing at meiosis / RHOBTB3 ATPase cycle / cyclin-dependent protein serine/threonine kinase regulator activity / G1/S-Specific Transcription / 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 / Association of TriC/CCT with target proteins during biosynthesis / 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 / DNA replication initiation / cellular response to nitric oxide / cyclin-dependent protein kinase holoenzyme complex / positive regulation of G1/S transition of mitotic cell cycle / cyclin-dependent kinase / cyclin-dependent protein serine/threonine kinase activity / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / 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 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 / telomere maintenance / cyclin binding / post-translational protein modification / : / meiotic cell cycle / positive regulation of DNA replication / male germ cell nucleus / potassium ion transport / DNA Damage/Telomere Stress Induced Senescence / G1/S transition of mitotic cell cycle / CDK-mediated phosphorylation and removal of Cdc6 / SCF(Skp2)-mediated degradation of p27/p21 / Meiotic recombination / Wnt signaling pathway / Orc1 removal from chromatin / Transcriptional regulation of granulopoiesis / Cyclin D associated events in G1 / regulation of protein localization / G2/M transition of mitotic cell cycle / cellular senescence / Regulation of TP53 Degradation / nuclear envelope / kinase activity / 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 / Regulation of TP53 Activity through Phosphorylation / DNA replication / Ras protein signal transduction / transcription regulator complex / chromosome, telomeric region / endosome / chromatin remodeling / protein domain specific binding / cell division / protein phosphorylation / protein serine kinase activity / DNA repair / protein serine/threonine kinase activity / centrosome / DNA-templated transcription / positive regulation of cell population proliferation / protein kinase binding / 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: 3 Å | ||||||
Authors | Ren, X. | ||||||
Funding support | 1items
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Citation | Journal: Acs Med.Chem.Lett. / Year: 2023 Title: Accelerated Discovery of Macrocyclic CDK2 Inhibitor QR-6401 by Generative Models and Structure-Based Drug Design. Authors: Yu, Y. / Huang, J. / He, H. / Han, J. / Ye, G. / Xu, T. / Sun, X. / Chen, X. / Ren, X. / Li, C. / Li, H. / Huang, W. / Liu, Y. / Wang, X. / Gao, Y. / Cheng, N. / Guo, N. / Chen, X. / Feng, J. ...Authors: Yu, Y. / Huang, J. / He, H. / Han, J. / Ye, G. / Xu, T. / Sun, X. / Chen, X. / Ren, X. / Li, C. / Li, H. / Huang, W. / Liu, Y. / Wang, X. / Gao, Y. / Cheng, N. / Guo, N. / Chen, X. / Feng, J. / Hua, Y. / Liu, C. / Zhu, G. / Xie, Z. / Yao, L. / Zhong, W. / Chen, X. / Liu, W. / Li, H. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8h6t.cif.gz | 131.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8h6t.ent.gz | 99.8 KB | Display | PDB format |
PDBx/mmJSON format | 8h6t.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/h6/8h6t ftp://data.pdbj.org/pub/pdb/validation_reports/h6/8h6t | HTTPS FTP |
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-Related structure data
Related structure data | 8h6pC 1w98S 8h6o C: citing same article (ref.) S: Starting model for refinement |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 34040.426 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CDK2, CDKN2 / Production host: Escherichia coli (E. coli) / References: UniProt: P24941, cyclin-dependent kinase |
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#2: Protein | Mass: 31712.877 Da / Num. of mol.: 1 / Fragment: Residues 103-373 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CCNE1, CCNE / Production host: Escherichia coli (E. coli) / References: UniProt: P24864 |
#3: Chemical | ChemComp-WZZ / ( |
#4: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3 Å3/Da / Density % sol: 58.99 % |
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Crystal grow | Temperature: 291.15 K / Method: vapor diffusion, hanging drop / Details: 0.2 M sodium citrate pH 6.5, 10% PEG3350 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SSRF / Beamline: BL02U1 / Wavelength: 1 Å |
Detector | Type: DECTRIS EIGER2 S 9M / Detector: PIXEL / Date: Dec 15, 2021 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 3→45.32 Å / Num. obs: 16618 / % possible obs: 97.91 % / Redundancy: 2 % / CC1/2: 1 / CC star: 1 / Rmerge(I) obs: 0.02245 / Rpim(I) all: 0.02245 / Rrim(I) all: 0.03175 / Net I/σ(I): 15.77 |
Reflection shell | Resolution: 3→3.107 Å / Rmerge(I) obs: 0.3028 / Mean I/σ(I) obs: 2.33 / Num. unique obs: 1612 / CC1/2: 0.894 / CC star: 0.972 / Rpim(I) all: 0.3028 / Rrim(I) all: 0.4283 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1W98 Resolution: 3→45.32 Å / Cor.coef. Fo:Fc: 0.922 / Cor.coef. Fo:Fc free: 0.766 / SU B: 31.511 / SU ML: 0.53 / Cross valid method: THROUGHOUT / ESU R Free: 0.602 / 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: 86.146 Å2
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Refinement step | Cycle: 1 / Resolution: 3→45.32 Å
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Refine LS restraints |
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