+Open data
-Basic information
Entry | Database: PDB / ID: 8bsm | ||||||
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Title | Human GLS in complex with compound 18 | ||||||
Components | Glutaminase kidney isoform, mitochondrial 65 kDa chain | ||||||
Keywords | HYDROLASE / GLUTAMINASE / Thiadiazole / Pyridazine / Inhibitor | ||||||
Function / homology | Function and homology information glutamine catabolic process / glutamate biosynthetic process / regulation of respiratory gaseous exchange by nervous system process / Glutamate and glutamine metabolism / intracellular glutamate homeostasis / Glutamate Neurotransmitter Release Cycle / glutaminase / glutaminase activity / suckling behavior / TP53 Regulates Metabolic Genes ...glutamine catabolic process / glutamate biosynthetic process / regulation of respiratory gaseous exchange by nervous system process / Glutamate and glutamine metabolism / intracellular glutamate homeostasis / Glutamate Neurotransmitter Release Cycle / glutaminase / glutaminase activity / suckling behavior / TP53 Regulates Metabolic Genes / chemical synaptic transmission / protein homotetramerization / mitochondrial matrix / synapse / mitochondrion / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.782 Å | ||||||
Authors | Debreczeni, J.E. | ||||||
Funding support | 1items
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Citation | Journal: J Med Chem / Year: 2019 Title: Discovery of a Thiadiazole-Pyridazine-Based Allosteric Glutaminase 1 Inhibitor Series That Demonstrates Oral Bioavailability and Activity in Tumor Xenograft Models. Authors: Finlay, M.R.V. / Anderton, M. / Bailey, A. / Boyd, S. / Brookfield, J. / Cairnduff, C. / Charles, M. / Cheasty, A. / Critchlow, S.E. / Culshaw, J. / Ekwuru, T. / Hollingsworth, I. / Jones, N. ...Authors: Finlay, M.R.V. / Anderton, M. / Bailey, A. / Boyd, S. / Brookfield, J. / Cairnduff, C. / Charles, M. / Cheasty, A. / Critchlow, S.E. / Culshaw, J. / Ekwuru, T. / Hollingsworth, I. / Jones, N. / Leroux, F. / Littleson, M. / McCarron, H. / McKelvie, J. / Mooney, L. / Nissink, J.W.M. / Perkins, D. / Powell, S. / Quesada, M.J. / Raubo, P. / Sabin, V. / Smith, J. / Smith, P.D. / Stark, A. / Ting, A. / Wang, P. / Wilson, Z. / Winter-Holt, J.J. / Wood, J.M. / Wrigley, G.L. / Yu, G. / Zhang, P. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8bsm.cif.gz | 131.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8bsm.ent.gz | 105.2 KB | Display | PDB format |
PDBx/mmJSON format | 8bsm.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/bs/8bsm ftp://data.pdbj.org/pub/pdb/validation_reports/bs/8bsm | HTTPS FTP |
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-Related structure data
Related structure data | 8bskC 8bslC 8bsnC C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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Components on special symmetry positions |
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-Components
#1: Protein | Mass: 34688.613 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GLS, GLS1, KIAA0838 / Organ: kidney / Production host: Escherichia coli BL21 (bacteria) / References: UniProt: O94925 | ||||||
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#2: Chemical | ChemComp-SO4 / #3: Chemical | ChemComp-5XX / | #4: Water | ChemComp-HOH / | Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.5 / Details: 1.8M Lithium sulphate 0.1M BisTris pH 6.5 |
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-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I04-1 / Wavelength: 0.92 Å |
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Dec 13, 2012 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.92 Å / Relative weight: 1 |
Reflection | Resolution: 2.78→40 Å / Num. obs: 19775 / % possible obs: 99.9 % / Redundancy: 10.1 % / Rmerge(I) obs: 0.116 / Rpim(I) all: 0.038 / Rrim(I) all: 0.122 / Net I/σ(I): 14.2 |
Reflection shell | Resolution: 2.78→3 Å / Redundancy: 9.7 % / Rmerge(I) obs: 0.608 / Mean I/σ(I) obs: 3.6 / Num. unique obs: 4025 / Rpim(I) all: 0.214 / Rrim(I) all: 0.679 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.782→40.01 Å / Cor.coef. Fo:Fc: 0.925 / Cor.coef. Fo:Fc free: 0.926 / SU R Cruickshank DPI: 0.285 / Cross valid method: THROUGHOUT / SU R Blow DPI: 0.299 / SU Rfree Blow DPI: 0.219 / SU Rfree Cruickshank DPI: 0.216
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Displacement parameters | Biso mean: 59.39 Å2
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Refine analyze | Luzzati coordinate error obs: 0.35 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.782→40.01 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.782→2.8 Å
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Refinement TLS params. | Origin x: -7.199 Å / Origin y: 15.5401 Å / Origin z: 23.5427 Å
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Refinement TLS group | Selection details: { A|* } |