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Yorodumi- PDB-6bky: Novel Binding Modes of Inhibition of Wild-Type IDH1: Allosteric I... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6bky | ||||||
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Title | Novel Binding Modes of Inhibition of Wild-Type IDH1: Allosteric Inhibition with Cmpd2 | ||||||
Components | Isocitrate dehydrogenase [NADP] cytoplasmic | ||||||
Keywords | OXIDOREDUCTASE/OXIDOREDUCTASE inhibitor / dehydrogenase / inhibitor / OXIDOREDUCTASE / OXIDOREDUCTASE-OXIDOREDUCTASE inhibitor complex | ||||||
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: 2.17 Å | ||||||
Authors | Jakob, C.G. / Qiu, W. | ||||||
Citation | Journal: J. Med. Chem. / Year: 2018 Title: Novel Modes of Inhibition of Wild-Type Isocitrate Dehydrogenase 1 (IDH1): Direct Covalent Modification of His315. Authors: Jakob, C.G. / Upadhyay, A.K. / Donner, P.L. / Nicholl, E. / Addo, S.N. / Qiu, W. / Ling, C. / Gopalakrishnan, S.M. / Torrent, M. / Cepa, S.P. / Shanley, J. / Shoemaker, A.R. / Sun, C.C. / ...Authors: Jakob, C.G. / Upadhyay, A.K. / Donner, P.L. / Nicholl, E. / Addo, S.N. / Qiu, W. / Ling, C. / Gopalakrishnan, S.M. / Torrent, M. / Cepa, S.P. / Shanley, J. / Shoemaker, A.R. / Sun, C.C. / Vasudevan, A. / Woller, K.R. / Shotwell, J.B. / Shaw, B. / Bian, Z. / Hutti, J.E. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6bky.cif.gz | 518.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6bky.ent.gz | 424.1 KB | Display | PDB format |
PDBx/mmJSON format | 6bky.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/bk/6bky ftp://data.pdbj.org/pub/pdb/validation_reports/bk/6bky | HTTPS FTP |
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-Related structure data
Related structure data | 6bkxC 6bkzC 6bl0C 6bl1C 6bl2C 4umxS 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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2 |
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3 |
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Unit cell |
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-Components
#1: Protein | Mass: 48154.730 Da / Num. of mol.: 6 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+) #2: Chemical | #3: Chemical | ChemComp-MG / #4: Chemical | #5: 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: 2.82 Å3/Da / Density % sol: 56.39 % |
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Crystal grow | Temperature: 290 K / Method: vapor diffusion / pH: 7 / Details: 20% PEG3350, 0.15M D,L-Malic acid pH 7.0 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Oct 8, 2015 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.17→137.44 Å / Num. obs: 159602 / % possible obs: 97.9 % / Redundancy: 3.4 % / Biso Wilson estimate: 44.17 Å2 / Rmerge(I) obs: 0.084 / Net I/σ(I): 10.1 |
Reflection shell | Resolution: 2.171→2.179 Å / Redundancy: 3.6 % / Rmerge(I) obs: 0.715 / Mean I/σ(I) obs: 2.1 / Num. unique obs: 1667 / % possible all: 96 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4UMX Resolution: 2.17→137.44 Å / Cor.coef. Fo:Fc: 0.949 / Cor.coef. Fo:Fc free: 0.928 / SU R Cruickshank DPI: 0.214 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.214 / SU Rfree Blow DPI: 0.174 / SU Rfree Cruickshank DPI: 0.175 Details: Note that space group C2 was selected because one ligand was on a 2 fold symmetry axis.
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Displacement parameters | Biso mean: 46.28 Å2
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Refine analyze | Luzzati coordinate error obs: 0.28 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: 1 / Resolution: 2.17→137.44 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.17→2.23 Å / Total num. of bins used: 20
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