+Open data
-Basic information
Entry | Database: PDB / ID: 7o83 | ||||||
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Title | KRasG12C ligand complex | ||||||
Components | V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog, isoform CRA_b | ||||||
Keywords | SIGNALING PROTEIN / Inhibitor complex | ||||||
Function / homology | Function and homology information endocrine signaling / forebrain astrocyte development / negative regulation of epithelial cell differentiation / regulation of synaptic transmission, GABAergic / epithelial tube branching involved in lung morphogenesis / type I pneumocyte differentiation / Rac protein signal transduction / skeletal muscle cell differentiation / positive regulation of Rac protein signal transduction / glial cell proliferation ...endocrine signaling / forebrain astrocyte development / negative regulation of epithelial cell differentiation / regulation of synaptic transmission, GABAergic / epithelial tube branching involved in lung morphogenesis / type I pneumocyte differentiation / Rac protein signal transduction / skeletal muscle cell differentiation / positive regulation of Rac protein signal transduction / glial cell proliferation / protein-membrane adaptor activity / positive regulation of glial cell proliferation / homeostasis of number of cells within a tissue / striated muscle cell differentiation / regulation of long-term neuronal synaptic plasticity / visual learning / actin cytoskeleton organization / neuron apoptotic process / negative regulation of neuron apoptotic process / GTPase activity / positive regulation of gene expression / GTP binding / membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.38 Å | ||||||
Authors | Phillips, C. / Breed, J. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2022 Title: Discovery of AZD4625, a Covalent Allosteric Inhibitor of the Mutant GTPase KRAS G12C . Authors: Kettle, J.G. / Bagal, S.K. / Bickerton, S. / Bodnarchuk, M.S. / Boyd, S. / Breed, J. / Carbajo, R.J. / Cassar, D.J. / Chakraborty, A. / Cosulich, S. / Cumming, I. / Davies, M. / Davies, N.L. ...Authors: Kettle, J.G. / Bagal, S.K. / Bickerton, S. / Bodnarchuk, M.S. / Boyd, S. / Breed, J. / Carbajo, R.J. / Cassar, D.J. / Chakraborty, A. / Cosulich, S. / Cumming, I. / Davies, M. / Davies, N.L. / Eatherton, A. / Evans, L. / Feron, L. / Fillery, S. / Gleave, E.S. / Goldberg, F.W. / Hanson, L. / Harlfinger, S. / Howard, M. / Howells, R. / Jackson, A. / Kemmitt, P. / Lamont, G. / Lamont, S. / Lewis, H.J. / Liu, L. / Niedbala, M.J. / Phillips, C. / Polanski, R. / Raubo, P. / Robb, G. / Robinson, D.M. / Ross, S. / Sanders, M.G. / Tonge, M. / Whiteley, R. / Wilkinson, S. / Yang, J. / Zhang, W. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7o83.cif.gz | 82 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7o83.ent.gz | 64.4 KB | Display | PDB format |
PDBx/mmJSON format | 7o83.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/o8/7o83 ftp://data.pdbj.org/pub/pdb/validation_reports/o8/7o83 | HTTPS FTP |
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-Related structure data
Related structure data | 7o70C 7oo7C 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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2 |
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Unit cell |
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-Components
-Protein , 1 types, 2 molecules AB
#1: Protein | Mass: 19094.490 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KRAS, hCG_14731 / Production host: Escherichia coli (E. coli) / References: UniProt: A0A024RAV5 |
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-Non-polymers , 5 types, 92 molecules
#2: Chemical | #3: Chemical | #4: Chemical | #5: Chemical | ChemComp-CA / | #6: 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: 2.18 Å3/Da / Density % sol: 43.62 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / Details: 50mM HEPES, 100mM NaCl, 2mM MgSO4 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 1 Å |
Detector | Type: DECTRIS EIGER R 4M / Detector: PIXEL / Date: Mar 1, 2017 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.38→38 Å / Num. obs: 11933 / % possible obs: 97.4 % / Redundancy: 2.1 % / Rmerge(I) obs: 0.03 / Net I/σ(I): 10.1 |
Reflection shell | Resolution: 2.38→2.44 Å / Rmerge(I) obs: 0.55 / Num. unique obs: 853 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: na Resolution: 2.38→37.85 Å / Cor.coef. Fo:Fc: 0.908 / Cor.coef. Fo:Fc free: 0.835 / SU B: 9.885 / SU ML: 0.234 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 1.616 / ESU R Free: 0.35 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 66.75 Å2 / Biso mean: 17.425 Å2 / Biso min: 0.5 Å2
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Refinement step | Cycle: final / Resolution: 2.38→37.85 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.38→2.442 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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