+Open data
-Basic information
Entry | Database: PDB / ID: 6gzh | ||||||
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Title | Crystal Structure of Human CDK9/cyclinT1 with A86 | ||||||
Components |
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Keywords | TRANSFERASE / CDK9 / kinase inhibitor / A86 | ||||||
Function / homology | Function and homology information P-TEFb complex / Interactions of Tat with host cellular proteins / 7SK snRNA binding / cyclin/CDK positive transcription elongation factor complex / regulation of muscle cell differentiation / regulation of mRNA 3'-end processing / positive regulation of protein localization to chromatin / nucleus localization / cyclin-dependent protein serine/threonine kinase activator activity / positive regulation by host of viral transcription ...P-TEFb complex / Interactions of Tat with host cellular proteins / 7SK snRNA binding / cyclin/CDK positive transcription elongation factor complex / regulation of muscle cell differentiation / regulation of mRNA 3'-end processing / positive regulation of protein localization to chromatin / nucleus localization / cyclin-dependent protein serine/threonine kinase activator activity / positive regulation by host of viral transcription / RNA polymerase binding / positive regulation of DNA-templated transcription, elongation / negative regulation of protein localization to chromatin / [RNA-polymerase]-subunit kinase / transcription elongation-coupled chromatin remodeling / replication fork processing / regulation of cyclin-dependent protein serine/threonine kinase activity / cellular response to cytokine stimulus / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / RNA polymerase II transcribes snRNA genes / Tat-mediated elongation of the HIV-1 transcript / Formation of HIV-1 elongation complex containing HIV-1 Tat / cyclin-dependent kinase / Formation of HIV elongation complex in the absence of HIV Tat / cyclin-dependent protein serine/threonine kinase activity / regulation of DNA repair / RNA Polymerase II Transcription Elongation / Formation of RNA Pol II elongation complex / RNA Polymerase II Pre-transcription Events / RNA polymerase II CTD heptapeptide repeat kinase activity / transcription elongation factor complex / molecular condensate scaffold activity / transcription elongation by RNA polymerase II / transcription initiation at RNA polymerase II promoter / TP53 Regulates Transcription of DNA Repair Genes / positive regulation of transcription elongation by RNA polymerase II / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / PML body / transcription coactivator binding / cytoplasmic ribonucleoprotein granule / kinase activity / DNA-binding transcription factor binding / Estrogen-dependent gene expression / cell population proliferation / transcription by RNA polymerase II / transcription cis-regulatory region binding / regulation of cell cycle / protein kinase activity / response to xenobiotic stimulus / cell cycle / RNA polymerase II cis-regulatory region sequence-specific DNA binding / cell division / protein phosphorylation / protein serine kinase activity / DNA repair / protein serine/threonine kinase activity / chromatin binding / regulation of transcription by RNA polymerase II / protein kinase binding / positive regulation of transcription by RNA polymerase II / DNA binding / nucleoplasm / ATP binding / membrane / nucleus / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.17 Å | ||||||
Authors | Ben-neriah, Y. / Venkatachalam, A. / Minzel, W. / Fink, A. / Snir-Alkalay, I. / Vacca, J. | ||||||
Citation | Journal: Cell / Year: 2018 Title: Small Molecules Co-targeting CKI alpha and the Transcriptional Kinases CDK7/9 Control AML in Preclinical Models. Authors: Minzel, W. / Venkatachalam, A. / Fink, A. / Hung, E. / Brachya, G. / Burstain, I. / Shaham, M. / Rivlin, A. / Omer, I. / Zinger, A. / Elias, S. / Winter, E. / Erdman, P.E. / Sullivan, R.W. / ...Authors: Minzel, W. / Venkatachalam, A. / Fink, A. / Hung, E. / Brachya, G. / Burstain, I. / Shaham, M. / Rivlin, A. / Omer, I. / Zinger, A. / Elias, S. / Winter, E. / Erdman, P.E. / Sullivan, R.W. / Fung, L. / Mercurio, F. / Li, D. / Vacca, J. / Kaushansky, N. / Shlush, L. / Oren, M. / Levine, R. / Pikarsky, E. / Snir-Alkalay, I. / Ben-Neriah, Y. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6gzh.cif.gz | 259.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6gzh.ent.gz | 205.7 KB | Display | PDB format |
PDBx/mmJSON format | 6gzh.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/gz/6gzh ftp://data.pdbj.org/pub/pdb/validation_reports/gz/6gzh | HTTPS FTP |
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-Related structure data
Related structure data | 6gzdC 6gzmC 3blhS 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: 37598.578 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CDK9, CDC2L4, TAK / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: P50750, cyclin-dependent kinase, [RNA-polymerase]-subunit kinase | ||
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#2: Protein | Mass: 80728.742 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CCNT1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: O60563 | ||
#3: Chemical | ChemComp-LCI / [ | ||
#4: Chemical | #5: 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: 3.84 Å3/Da / Density % sol: 68 % |
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Crystal grow | Temperature: 277.15 K / Method: vapor diffusion, sitting drop / pH: 7.3 Details: CDK9/Cyclin T1 at a concentration of 4.5 mg/ml (20 mM Tris / HCl, 250 mM NaCl, 1 mM DTT, 1 mM EDTA, pH 7.3) was pre-incubated with 0.6 mM (5.1-fold molar excess) of A-86 (150 mM in DMSO) and ...Details: CDK9/Cyclin T1 at a concentration of 4.5 mg/ml (20 mM Tris / HCl, 250 mM NaCl, 1 mM DTT, 1 mM EDTA, pH 7.3) was pre-incubated with 0.6 mM (5.1-fold molar excess) of A-86 (150 mM in DMSO) and 4 mM TCEP for 1 h. 0.1 ul of the protein solution was then mixed 0.1 ul of reservoir solution (0.01 M Ca-Chloride, 0.1 M MES/NaOH, pH 6.50, 1.2 M Na-Acetate) and equilibrated at 4 C over 0.06 ml of reservoir solution. Crystals were obtained using microseeding. Well diffracting crystals appeared within 4 days and grew to full size over 8 days |
-Data collection
Diffraction | Mean temperature: 100.15 K |
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: MASSIF-1 / Wavelength: 0.966 Å |
Detector | Type: DECTRIS PILATUS3 2M / Detector: PIXEL / Date: Mar 2, 2017 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.966 Å / Relative weight: 1 |
Reflection | Resolution: 3.17→30 Å / Num. obs: 16344 / % possible obs: 89.7 % / Redundancy: 1.5 % / Rrim(I) all: 0.156 / Net I/σ(I): 3.6 |
Reflection shell | Resolution: 3.17→3.34 Å / Redundancy: 1.4 % / Mean I/σ(I) obs: 1.1 / Num. unique obs: 2244 / Rrim(I) all: 0.702 / % possible all: 83.7 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3BLH Resolution: 3.17→30 Å / Cor.coef. Fo:Fc: 0.956 / Cor.coef. Fo:Fc free: 0.901 / SU B: 49.844 / SU ML: 0.418 / Cross valid method: THROUGHOUT / ESU R Free: 0.481 / 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: 86.514 Å2
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Refinement step | Cycle: 1 / Resolution: 3.17→30 Å
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