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Yorodumi- PDB-4v25: VER-246608, a novel pan-isoform ATP competitive inhibitor of pyru... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4v25 | ||||||
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Title | VER-246608, a novel pan-isoform ATP competitive inhibitor of pyruvate dehydrogenase kinase, disrupts Warburg metabolism and induces context- dependent cytostasis in cancer cells | ||||||
Components | [PYRUVATE DEHYDROGENASE (ACETYL-TRANSFERRING)] KINASE ISOZYME 2, MITOCHONDRIAL | ||||||
Keywords | TRANSFERASE / GLYCOLYSIS / WARBURG METABOLISM / NOV3R | ||||||
Function / homology | Function and homology information [pyruvate dehydrogenase (acetyl-transferring)] kinase / regulation of acetyl-CoA biosynthetic process from pyruvate / pyruvate dehydrogenase (acetyl-transferring) kinase activity / Regulation of pyruvate dehydrogenase (PDH) complex / pyruvate dehydrogenase complex / regulation of cellular ketone metabolic process / regulation of pH / cellular response to nutrient / Signaling by Retinoic Acid / regulation of gluconeogenesis ...[pyruvate dehydrogenase (acetyl-transferring)] kinase / regulation of acetyl-CoA biosynthetic process from pyruvate / pyruvate dehydrogenase (acetyl-transferring) kinase activity / Regulation of pyruvate dehydrogenase (PDH) complex / pyruvate dehydrogenase complex / regulation of cellular ketone metabolic process / regulation of pH / cellular response to nutrient / Signaling by Retinoic Acid / regulation of gluconeogenesis / intrinsic apoptotic signaling pathway by p53 class mediator / regulation of glucose metabolic process / regulation of calcium-mediated signaling / cellular response to reactive oxygen species / glucose metabolic process / glucose homeostasis / insulin receptor signaling pathway / protein kinase activity / mitochondrial matrix / protein homodimerization activity / mitochondrion / nucleoplasm / ATP binding / cytosol Similarity search - Function | ||||||
Biological species | HOMO SAPIENS (human) | ||||||
Method | X-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.6 Å | ||||||
Authors | Moore, J.D. / Staniszewska, A. / Shaw, T. / D'Alessandro, J. / Davis, B. / Surgenor, A. / Baker, L. / Matassova, N. / Murray, J. / Macias, A. ...Moore, J.D. / Staniszewska, A. / Shaw, T. / D'Alessandro, J. / Davis, B. / Surgenor, A. / Baker, L. / Matassova, N. / Murray, J. / Macias, A. / Brough, P. / Wood, M. / Mahon, P.C. | ||||||
Citation | Journal: Oncotarget / Year: 2014 Title: VER-246608, a novel pan-isoform ATP competitive inhibitor of pyruvate dehydrogenase kinase, disrupts Warburg metabolism and induces context-dependent cytostasis in cancer cells. Authors: Moore, J.D. / Staniszewska, A. / Shaw, T. / D'Alessandro, J. / Davis, B. / Surgenor, A. / Baker, L. / Matassova, N. / Murray, J. / Macias, A. / Brough, P. / Wood, M. / Mahon, P.C. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4v25.cif.gz | 87.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4v25.ent.gz | 65.6 KB | Display | PDB format |
PDBx/mmJSON format | 4v25.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/v2/4v25 ftp://data.pdbj.org/pub/pdb/validation_reports/v2/4v25 | HTTPS FTP |
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-Related 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: 46290.727 Da / Num. of mol.: 1 / Fragment: KINASE DOMAIN Source method: isolated from a genetically manipulated source Source: (gene. exp.) HOMO SAPIENS (human) / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3) References: UniProt: Q15119, [pyruvate dehydrogenase (acetyl-transferring)] kinase |
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#2: Chemical | ChemComp-TF3 / |
#3: Chemical | ChemComp-MG / |
#4: Chemical | ChemComp-SZ6 / |
#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: 3.12 Å3/Da / Density % sol: 60.61 % / Description: NONE |
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Crystal grow | pH: 5.8 Details: 0.1 M SODIUM ACETATE PH 5.8, 0.125 M MAGNESIUM CHLORIDE AND 6% ISOPROPANOL, 4OC |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU RUH3R / Wavelength: 1.5418 |
Detector | Type: RIGAKU RAXIS4 / Detector: IMAGE PLATE / Date: Oct 23, 2012 / Details: OSMIC BLUE |
Radiation | Monochromator: CU FILTER / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 2.6→30 Å / Num. obs: 17281 / % possible obs: 98.3 % / Observed criterion σ(I): 1.5 / Redundancy: 2.31 % / Rmerge(I) obs: 0.12 / Net I/σ(I): 5 |
Reflection shell | Resolution: 2.6→2.69 Å / Redundancy: 2.19 % / Rmerge(I) obs: 0.53 / Mean I/σ(I) obs: 1.3 / % possible all: 97.7 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: APO PDK2 Resolution: 2.6→25.01 Å / Cor.coef. Fo:Fc: 0.954 / Cor.coef. Fo:Fc free: 0.93 / SU B: 12.022 / SU ML: 0.241 / Cross valid method: THROUGHOUT / ESU R: 0.405 / ESU R Free: 0.286 / 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: 63.207 Å2
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Refinement step | Cycle: LAST / Resolution: 2.6→25.01 Å
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Refine LS restraints |
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