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Yorodumi- PDB-6vei: Crystal Structure of Human Cytosolic Isocitrate Dehydrogenase (ID... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6vei | ||||||
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Title | Crystal Structure of Human Cytosolic Isocitrate Dehydrogenase (IDH1) R132H Mutant in Complex with NADPH and AG-881 (Vorasidenib) Inhibitor | ||||||
Components | Isocitrate dehydrogenase [NADP] cytoplasmic | ||||||
Keywords | ANTITUMOR PROTEIN / IDH / CYTOSOLIC NADP-ISOCITRATE DEHYDROGENASE / OXALOSUCCINATE DECARBOXYLASE / NADP(+)-SPECIFIC ICDH / IDP | ||||||
Function / homology | Function and homology information Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate / NADPH regeneration / regulation of phospholipid catabolic process / regulation of phospholipid biosynthetic process / NFE2L2 regulating TCA cycle genes / isocitrate metabolic process / isocitrate dehydrogenase (NADP+) / isocitrate dehydrogenase (NADP+) activity / 2-oxoglutarate metabolic process / NADP metabolic process ...Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate / NADPH regeneration / regulation of phospholipid catabolic process / regulation of phospholipid biosynthetic process / NFE2L2 regulating TCA cycle genes / isocitrate metabolic process / isocitrate dehydrogenase (NADP+) / isocitrate dehydrogenase (NADP+) activity / 2-oxoglutarate metabolic process / NADP metabolic process / glyoxylate cycle / response to steroid hormone / female gonad development / peroxisomal matrix / tricarboxylic acid cycle / glutathione metabolic process / Peroxisomal protein import / peroxisome / NAD binding / tertiary granule lumen / NADP binding / secretory granule lumen / ficolin-1-rich granule lumen / response to oxidative stress / cadherin binding / Neutrophil degranulation / magnesium ion binding / protein homodimerization activity / mitochondrion / extracellular exosome / extracellular region / identical protein binding / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.1 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 | 6vei.cif.gz | 452.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6vei.ent.gz | 306.7 KB | Display | PDB format |
PDBx/mmJSON format | 6vei.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6vei_validation.pdf.gz | 621.7 KB | Display | wwPDB validaton report |
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Full document | 6vei_full_validation.pdf.gz | 626.7 KB | Display | |
Data in XML | 6vei_validation.xml.gz | 3.2 KB | Display | |
Data in CIF | 6vei_validation.cif.gz | 15.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ve/6vei ftp://data.pdbj.org/pub/pdb/validation_reports/ve/6vei | HTTPS FTP |
-Related structure data
Related structure data | 6vfzC 6vg0C 3inmS 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: 48135.684 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: IDH1, PICD / Production host: Escherichia coli (E. coli) References: UniProt: O75874, isocitrate dehydrogenase (NADP+) |
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-Non-polymers , 9 types, 650 molecules
#2: Chemical | #3: Chemical | ChemComp-SO4 / | #4: Chemical | ChemComp-33O / | #5: Chemical | ChemComp-PEG / #6: Chemical | ChemComp-ACT / | #7: Chemical | ChemComp-MLA / | #8: Chemical | ChemComp-9UO / | #9: Chemical | ChemComp-MLT / | #10: Water | ChemComp-HOH / | |
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-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: 2.5 Å3/Da / Density % sol: 50.88 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 4 / Details: 20% PEG 3350, 8% Tacsimate pH 4.0 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SSRF / Beamline: BL17B1 / Wavelength: 0.97915 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Jul 4, 2015 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97915 Å / Relative weight: 1 |
Reflection | Resolution: 2.1→50 Å / Num. obs: 57133 / % possible obs: 99.8 % / Redundancy: 7.1 % / Biso Wilson estimate: 27.15 Å2 / Rmerge(I) obs: 0.101 / Net I/σ(I): 9.5 |
Reflection shell | Resolution: 2.1→2.14 Å / Redundancy: 7.2 % / Rmerge(I) obs: 0.476 / Num. unique obs: 2817 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3INM Resolution: 2.1→35.51 Å / SU ML: 0.183 / Cross valid method: FREE R-VALUE / σ(F): 0 / Phase error: 17.7263 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: 29.6 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.1→35.51 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: 32.8781702682 Å / Origin y: 21.6314184266 Å / Origin z: 28.2429674266 Å
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Refinement TLS group | Selection details: all |