+Open data
-Basic information
Entry | Database: PDB / ID: 6p8h | |||||||||
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Title | Crystal structure of CDK4 in complex with CyclinD1 and P21 | |||||||||
Components |
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Keywords | cell cycle / transferase / Cyclin-dependent kinase / kinase inhibitor | |||||||||
Function / homology | Function and homology information cyclin-dependent protein kinase activating kinase activity / re-entry into mitotic cell cycle / cyclin D3-CDK4 complex / cyclin D1-CDK4 complex / cyclin D2-CDK4 complex / Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 / Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 / negative regulation of cardiac muscle tissue regeneration / negative regulation of cyclin-dependent protein kinase activity / cellular response to ionomycin ...cyclin-dependent protein kinase activating kinase activity / re-entry into mitotic cell cycle / cyclin D3-CDK4 complex / cyclin D1-CDK4 complex / cyclin D2-CDK4 complex / Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 / Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 / negative regulation of cardiac muscle tissue regeneration / negative regulation of cyclin-dependent protein kinase activity / cellular response to ionomycin / regulation of transcription initiation by RNA polymerase II / Drug-mediated inhibition of CDK4/CDK6 activity / Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6 / Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6 / regulation of type B pancreatic cell proliferation / RUNX3 regulates WNT signaling / response to leptin / FOXO-mediated transcription of cell cycle genes / TFAP2 (AP-2) family regulates transcription of cell cycle factors / PCNA-p21 complex / positive regulation of mammary gland epithelial cell proliferation / intestinal epithelial cell maturation / : / regulation of cell cycle G1/S phase transition / tissue regeneration / Transcriptional regulation by RUNX2 / cellular response to phorbol 13-acetate 12-myristate / negative regulation of phosphorylation / cyclin-dependent protein serine/threonine kinase inhibitor activity / negative regulation of DNA biosynthetic process / response to arsenic-containing substance / cyclin-dependent protein serine/threonine kinase activator activity / positive regulation of programmed cell death / oncogene-induced cell senescence / proline-rich region binding / Transcriptional activation of cell cycle inhibitor p21 / Regulation of RUNX1 Expression and Activity / RUNX3 regulates CDKN1A transcription / AKT phosphorylates targets in the cytosol / cyclin-dependent protein serine/threonine kinase regulator activity / mammary gland epithelial cell proliferation / response to UV-A / stress-induced premature senescence / DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / negative regulation of epithelial cell differentiation / response to aldosterone / negative regulation of G1/S transition of mitotic cell cycle / regulation of cyclin-dependent protein serine/threonine kinase activity / response to corticosterone / cellular response to UV-B / molecular function inhibitor activity / STAT5 activation downstream of FLT3 ITD mutants / protein kinase inhibitor activity / fat cell differentiation / p53-Dependent G1 DNA Damage Response / PTK6 Regulates Cell Cycle / Constitutive Signaling by AKT1 E17K in Cancer / regulation of G1/S transition of mitotic cell cycle / mitotic G2 DNA damage checkpoint signaling / negative regulation of vascular associated smooth muscle cell proliferation / Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) / RUNX3 regulates p14-ARF / positive regulation of cyclin-dependent protein serine/threonine kinase activity / keratinocyte proliferation / Transcriptional Regulation by VENTX / response to X-ray / replicative senescence / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / cyclin-dependent protein kinase holoenzyme complex / bicellular tight junction / response to hyperoxia / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / positive regulation of protein kinase activity / mammary gland alveolus development / positive regulation of G1/S transition of mitotic cell cycle / cellular response to interleukin-4 / cyclin-dependent kinase / animal organ regeneration / cyclin-dependent protein serine/threonine kinase activity / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / Cyclin E associated events during G1/S transition / Cyclin A:Cdk2-associated events at S phase entry / positive regulation of B cell proliferation / endoplasmic reticulum unfolded protein response / keratinocyte differentiation / mitotic G1 DNA damage checkpoint signaling / response to organonitrogen compound / protein sequestering activity / regulation of G2/M transition of mitotic cell cycle / positive regulation of G2/M transition of mitotic cell cycle / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / Signaling by FLT3 fusion proteins / cellular response to amino acid starvation / lactation / transcription repressor complex / cyclin binding / intrinsic apoptotic signaling pathway / : / negative regulation of protein phosphorylation / negative regulation of protein binding Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.19 Å | |||||||||
Authors | Guiley, K.Z. / Stevenson, J.W. / Lou, K. / Barkovich, K.J. / Bunch, K. / Tripathi, S.M. / Shokat, K.M. / Rubin, S.M. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Science / Year: 2019 Title: p27 allosterically activates cyclin-dependent kinase 4 and antagonizes palbociclib inhibition. Authors: Guiley, K.Z. / Stevenson, J.W. / Lou, K. / Barkovich, K.J. / Kumarasamy, V. / Wijeratne, T.U. / Bunch, K.L. / Tripathi, S. / Knudsen, E.S. / Witkiewicz, A.K. / Shokat, K.M. / Rubin, S.M. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6p8h.cif.gz | 238.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6p8h.ent.gz | 192 KB | Display | PDB format |
PDBx/mmJSON format | 6p8h.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6p8h_validation.pdf.gz | 441 KB | Display | wwPDB validaton report |
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Full document | 6p8h_full_validation.pdf.gz | 445.2 KB | Display | |
Data in XML | 6p8h_validation.xml.gz | 20.4 KB | Display | |
Data in CIF | 6p8h_validation.cif.gz | 26.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/p8/6p8h ftp://data.pdbj.org/pub/pdb/validation_reports/p8/6p8h | HTTPS FTP |
-Related structure data
Related structure data | 6p8eC 6p8fC 6p8gC 2w96S 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: 28445.293 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CCND1, BCL1, PRAD1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P24385 |
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#2: Protein | Mass: 33947.930 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CDK4 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P11802, cyclin-dependent kinase |
#3: Protein | Mass: 9087.271 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CDKN1A, CAP20, CDKN1, CIP1, MDA6, PIC1, SDI1, WAF1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P38936 |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.76 Å3/Da / Density % sol: 55.43 % |
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Crystal grow | Temperature: 295 K / Method: microbatch / pH: 7 / Details: 100mM Tris (7.0), 10% PEG 8000 200mM MgCl2 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 8.3.1 / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS3 S 6M / Detector: PIXEL / Date: Dec 15, 2017 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 3.19→92.68 Å / Num. obs: 13821 / % possible obs: 99.9 % / Redundancy: 5.9 % / CC1/2: 0.99 / Rmerge(I) obs: 0.167 / Rpim(I) all: 0.08 / Net I/σ(I): 9.2 |
Reflection shell | Resolution: 3.19→3.41 Å / Redundancy: 5.8 % / Mean I/σ(I) obs: 2.1 / Num. unique obs: 2439 / CC1/2: 0.75 / Rpim(I) all: 0.406 / Rsym value: 0.837 / % possible all: 99.8 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2W96 Resolution: 3.19→44.698 Å / SU ML: 0.43 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 27.1 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 3.19→44.698 Å
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Refine LS restraints |
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LS refinement shell |
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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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