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Yorodumi- PDB-6vfz: Crystal Structure of Human Mitochondrial Isocitrate Dehydrogenase... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6vfz | ||||||
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Title | Crystal Structure of Human Mitochondrial Isocitrate Dehydrogenase (IDH2) R140Q Mutant Homodimer in Complex with NADPH and AG-881 (Vorasidenib) Inhibitor. | ||||||
Components | Isocitrate dehydrogenase [NADP], mitochondrial | ||||||
Keywords | OXIDOREDUCTASE/OXIDOREDUCTASE inhibitor / IDH / ICD-M / IDP / NADP(+)-SPECIFIC ICDH / OXALOSUCCINATE DECARBOXYLASE / OXIDOREDUCTASE-OXIDOREDUCTASE inhibitor complex | ||||||
Function / homology | Function and homology information Citric acid cycle (TCA cycle) / isocitrate metabolic process / isocitrate dehydrogenase (NADP+) / isocitrate dehydrogenase (NADP+) activity / 2-oxoglutarate metabolic process / NADP metabolic process / glyoxylate cycle / tricarboxylic acid cycle / Mitochondrial protein degradation / Transcriptional activation of mitochondrial biogenesis ...Citric acid cycle (TCA cycle) / isocitrate metabolic process / isocitrate dehydrogenase (NADP+) / isocitrate dehydrogenase (NADP+) activity / 2-oxoglutarate metabolic process / NADP metabolic process / glyoxylate cycle / tricarboxylic acid cycle / Mitochondrial protein degradation / Transcriptional activation of mitochondrial biogenesis / peroxisome / NAD binding / carbohydrate metabolic process / mitochondrial matrix / magnesium ion binding / mitochondrion / extracellular exosome / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.99 Å | ||||||
Authors | Padyana, A. / Jin, L. | ||||||
Citation | Journal: Acs Med.Chem.Lett. / Year: 2020 Title: Vorasidenib (AG-881): A First-in-Class, Brain-Penetrant Dual Inhibitor of Mutant IDH1 and 2 for Treatment of Glioma. Authors: Konteatis, Z. / Artin, E. / Nicolay, B. / Straley, K. / Padyana, A.K. / Jin, L. / Chen, Y. / Narayaraswamy, R. / Tong, S. / Wang, F. / Zhou, D. / Cui, D. / Cai, Z. / Luo, Z. / Fang, C. / ...Authors: Konteatis, Z. / Artin, E. / Nicolay, B. / Straley, K. / Padyana, A.K. / Jin, L. / Chen, Y. / Narayaraswamy, R. / Tong, S. / Wang, F. / Zhou, D. / Cui, D. / Cai, Z. / Luo, Z. / Fang, C. / Tang, H. / Lv, X. / Nagaraja, R. / Yang, H. / Su, S.M. / Sui, Z. / Dang, L. / Yen, K. / Popovici-Muller, J. / Codega, P. / Campos, C. / Mellinghoff, I.K. / Biller, S.A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6vfz.cif.gz | 449.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6vfz.ent.gz | 308 KB | Display | PDB format |
PDBx/mmJSON format | 6vfz.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6vfz_validation.pdf.gz | 535.2 KB | Display | wwPDB validaton report |
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Full document | 6vfz_full_validation.pdf.gz | 538.7 KB | Display | |
Data in XML | 6vfz_validation.xml.gz | 2.4 KB | Display | |
Data in CIF | 6vfz_validation.cif.gz | 14.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vf/6vfz ftp://data.pdbj.org/pub/pdb/validation_reports/vf/6vfz | HTTPS FTP |
-Related structure data
Related structure data | 6veiC 6vg0C 5i96S C: citing same article (ref.) S: Starting model for refinement |
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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
-Protein , 1 types, 2 molecules AB
#1: Protein | Mass: 51783.008 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: IDH2 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: P48735, isocitrate dehydrogenase (NADP+) |
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-Non-polymers , 5 types, 623 molecules
#2: Chemical | ChemComp-9UO / | ||||||
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#3: Chemical | #4: Chemical | #5: Chemical | #6: Water | ChemComp-HOH / | |
-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.24 Å3/Da / Density % sol: 45.02 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop / pH: 8.5 Details: 200 mM CaCl2, 0.1M Tris-HCL pH8.5, 20% (w/v) PEG 4000 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SSRF / Beamline: BL19U1 / Wavelength: 0.97853 Å |
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Apr 29, 2015 |
Radiation | Monochromator: Pilatus 3 6M / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97853 Å / Relative weight: 1 |
Reflection | Resolution: 1.99→50 Å / Num. obs: 63731 / % possible obs: 100 % / Redundancy: 12.7 % / Biso Wilson estimate: 22.32 Å2 / Rmerge(I) obs: 0.095 / Net I/σ(I): 8.1 |
Reflection shell | Resolution: 1.99→2.03 Å / Redundancy: 9.9 % / Rmerge(I) obs: 0.905 / Num. unique obs: 3146 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5I96 Resolution: 1.99→42.06 Å / SU ML: 0.1541 / Cross valid method: FREE R-VALUE / σ(F): 1.38 / Phase error: 19.7411 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 34.23 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.99→42.06 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Origin x: -32.4603290885 Å / Origin y: 11.3263287318 Å / Origin z: -25.900576091 Å
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Refinement TLS group | Selection details: all |