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Yorodumi- PDB-5lge: Crystal Structure of human IDH1 mutant (R132H) in complex with NA... -
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-Basic information
Entry | Database: PDB / ID: 5lge | ||||||
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Title | Crystal Structure of human IDH1 mutant (R132H) in complex with NADP+ and an Inhibitor related to BAY 1436032 | ||||||
Components | Isocitrate dehydrogenase [NADP] cytoplasmic | ||||||
Keywords | OXIDOREDUCTASE / IDH1 / ALLOSTERIC INHIBITOR / NADP+ | ||||||
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 / glutathione metabolic process / tricarboxylic acid cycle / Peroxisomal protein import / peroxisome / NAD binding / tertiary granule lumen / NADP binding / secretory granule lumen / response to oxidative stress / ficolin-1-rich granule lumen / cadherin binding / Neutrophil degranulation / magnesium ion binding / protein homodimerization activity / mitochondrion / extracellular exosome / extracellular region / identical protein binding / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.7 Å | ||||||
Authors | Hillig, R.C. / Hars, U. / Korndoerfer, I.P. | ||||||
Citation | Journal: Acta Neuropathol. / Year: 2017 Title: Pan-mutant IDH1 inhibitor BAY 1436032 for effective treatment of IDH1 mutant astrocytoma in vivo. Authors: Pusch, S. / Krausert, S. / Fischer, V. / Balss, J. / Ott, M. / Schrimpf, D. / Capper, D. / Sahm, F. / Eisel, J. / Beck, A.C. / Jugold, M. / Eichwald, V. / Kaulfuss, S. / Panknin, O. / ...Authors: Pusch, S. / Krausert, S. / Fischer, V. / Balss, J. / Ott, M. / Schrimpf, D. / Capper, D. / Sahm, F. / Eisel, J. / Beck, A.C. / Jugold, M. / Eichwald, V. / Kaulfuss, S. / Panknin, O. / Rehwinkel, H. / Zimmermann, K. / Hillig, R.C. / Guenther, J. / Toschi, L. / Neuhaus, R. / Haegebart, A. / Hess-Stumpp, H. / Bauser, M. / Wick, W. / Unterberg, A. / Herold-Mende, C. / Platten, M. / von Deimling, A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5lge.cif.gz | 674.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5lge.ent.gz | 566.6 KB | Display | PDB format |
PDBx/mmJSON format | 5lge.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/lg/5lge ftp://data.pdbj.org/pub/pdb/validation_reports/lg/5lge | HTTPS FTP |
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-Related structure data
Related structure data | 4kzoS S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Component-ID: 0 / Beg auth comp-ID: LYS / Beg label comp-ID: LYS / Refine code: 0
NCS ensembles :
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-Components
-Protein , 1 types, 4 molecules ABCD
#1: Protein | Mass: 48135.684 Da / Num. of mol.: 4 / Mutation: R132H Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: IDH1, PICD / Plasmid: P10T7-2 / Production host: Escherichia coli (E. coli) / Variant (production host): RIL References: UniProt: O75874, isocitrate dehydrogenase (NADP+) |
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-Non-polymers , 5 types, 521 molecules
#2: Chemical | ChemComp-NAP / #3: Chemical | #4: Chemical | #5: Chemical | ChemComp-ACT / | #6: Water | ChemComp-HOH / | |
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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: 2.76 Å3/Da / Density % sol: 55.36 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion / pH: 7 Details: PROTEIN BUFFER: 15 MG/ML. PROTEIN IN 25 MM HEPES, 300 MM NACL, 5 MM BETA-ME, COMPLETE PROTEASE INHIBITOR MIXTURE, PH 7.7 RESERVOIR: 100 MM BIS-TRIS, PH 7.0, 200 MM CA-ACETATE, 20.0 %(W/V) PEG 3350 |
-Data collection
Diffraction | Mean temperature: 93 K |
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: ID29 / Wavelength: 0.976 Å |
Detector | Type: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Dec 16, 2013 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.976 Å / Relative weight: 1 |
Reflection | Resolution: 2.7→30 Å / Num. obs: 56625 / % possible obs: 98.7 % / Observed criterion σ(I): 2 / Redundancy: 4.8 % / Rmerge(I) obs: 0.12 / Net I/σ(I): 8.6 |
Reflection shell | Resolution: 2.7→2.85 Å / Redundancy: 4.8 % / Rmerge(I) obs: 0.7 / Mean I/σ(I) obs: 2.3 / % possible all: 99 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4KZO Resolution: 2.7→29.94 Å / Cor.coef. Fo:Fc: 0.949 / Cor.coef. Fo:Fc free: 0.927 / SU B: 25.881 / SU ML: 0.276 / Cross valid method: THROUGHOUT / ESU R Free: 0.321 / 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 73.2 Å2
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Refinement step | Cycle: 1 / Resolution: 2.7→29.94 Å
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Refine LS restraints |
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