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Yorodumi- PDB-6gqm: Crystal structure of human c-KIT kinase domain in complex with a ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6gqm | ||||||
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Title | Crystal structure of human c-KIT kinase domain in complex with a small molecule inhibitor, AZD3229 | ||||||
Components | Mast/stem cell growth factor receptor Kit | ||||||
Keywords | SIGNALING PROTEIN / receptor tyrosine kinase / inhibitor / oncology / gastrointestinal stromal tumour / structure-based drug design | ||||||
Function / homology | Function and homology information Protein tyrosine and serine/threonine kinase / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta Similarity search - Domain/homology | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2 Å | ||||||
Authors | Schimpl, M. / Hardy, C.J. / Ogg, D.J. / Overman, R.C. / Packer, M.J. / Kettle, J.G. / Anjum, R. / Barry, E. / Bhavsar, D. / Brown, C. ...Schimpl, M. / Hardy, C.J. / Ogg, D.J. / Overman, R.C. / Packer, M.J. / Kettle, J.G. / Anjum, R. / Barry, E. / Bhavsar, D. / Brown, C. / Campbell, A. / Goldberg, K. / Grondine, M. / Guichard, S. / Hunt, T. / Jones, O. / Li, X. / Moleva, O. / Pearson, S. / Shao, W. / Smith, A. / Smith, J. / Stead, D. / Stokes, S. / Tucker, M. / Ye, Y. | ||||||
Citation | Journal: J. Med. Chem. / Year: 2018 Title: Discovery of N-(4-{[5-Fluoro-7-(2-methoxyethoxy)quinazolin-4-yl]amino}phenyl)-2-[4-(propan-2-yl)-1 H-1,2,3-triazol-1-yl]acetamide (AZD3229), a Potent Pan-KIT Mutant Inhibitor for the Treatment ...Title: Discovery of N-(4-{[5-Fluoro-7-(2-methoxyethoxy)quinazolin-4-yl]amino}phenyl)-2-[4-(propan-2-yl)-1 H-1,2,3-triazol-1-yl]acetamide (AZD3229), a Potent Pan-KIT Mutant Inhibitor for the Treatment of Gastrointestinal Stromal Tumors. Authors: Kettle, J.G. / Anjum, R. / Barry, E. / Bhavsar, D. / Brown, C. / Boyd, S. / Campbell, A. / Goldberg, K. / Grondine, M. / Guichard, S. / Hardy, C.J. / Hunt, T. / Jones, R.D.O. / Li, X. / ...Authors: Kettle, J.G. / Anjum, R. / Barry, E. / Bhavsar, D. / Brown, C. / Boyd, S. / Campbell, A. / Goldberg, K. / Grondine, M. / Guichard, S. / Hardy, C.J. / Hunt, T. / Jones, R.D.O. / Li, X. / Moleva, O. / Ogg, D. / Overman, R.C. / Packer, M.J. / Pearson, S. / Schimpl, M. / Shao, W. / Smith, A. / Smith, J.M. / Stead, D. / Stokes, S. / Tucker, M. / Ye, Y. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6gqm.cif.gz | 253.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6gqm.ent.gz | 204.8 KB | Display | PDB format |
PDBx/mmJSON format | 6gqm.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6gqm_validation.pdf.gz | 811.7 KB | Display | wwPDB validaton report |
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Full document | 6gqm_full_validation.pdf.gz | 816 KB | Display | |
Data in XML | 6gqm_validation.xml.gz | 25 KB | Display | |
Data in CIF | 6gqm_validation.cif.gz | 35.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/gq/6gqm ftp://data.pdbj.org/pub/pdb/validation_reports/gq/6gqm | HTTPS FTP |
-Related structure data
Related structure data | 6gqjC 6gqkC 6gqlC 6gqoC 6gqpC 6gqqC 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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Unit cell |
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-Components
#1: Protein | Mass: 37332.578 Da / Num. of mol.: 2 Mutation: I563S, V569S, Y609Q, L631S, M651E, I662H, D768H, R804N, V825D, C844S, L890S, H894Y, L912D, L923D Source method: isolated from a genetically manipulated source Details: Human c-KIT kinase domain (P551-H934) bearing surface mutations to optimise protein expression (I563S, V569S, Y609Q, L631S, M651E, I662H, D768H, R804N, V825D, C844S, L890S, H894Y, L912D, ...Details: Human c-KIT kinase domain (P551-H934) bearing surface mutations to optimise protein expression (I563S, V569S, Y609Q, L631S, M651E, I662H, D768H, R804N, V825D, C844S, L890S, H894Y, L912D, L923D), and the kinase insert domain(S688-D765) deleted and replaced with the sequence EFVPYKVAPEDLYKDFLT Source: (gene. exp.) Homo sapiens (human) / Gene: KIT, SCFR / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): Star References: UniProt: P10721, receptor protein-tyrosine kinase #2: Chemical | #3: Chemical | #4: 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: 2.42 Å3/Da / Density % sol: 49.2 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.2 Details: 9 % PEG 8000, 18 % ethylene glycol, 0.1 M PCTP pH 6.2, 0.03 M sodium fluoride, 0.03 M sodium bromide, 0.03 M sodium iodide |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: SOLEIL / Beamline: PROXIMA 2 / Wavelength: 0.98007 Å |
Detector | Type: DECTRIS EIGER X 9M / Detector: PIXEL / Date: Oct 12, 2016 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.98007 Å / Relative weight: 1 |
Reflection | Resolution: 2→45.09 Å / Num. obs: 49740 / % possible obs: 99.8 % / Redundancy: 6.7 % / Biso Wilson estimate: 42.69 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.102 / Net I/σ(I): 11 |
Reflection shell | Resolution: 2→2.05 Å / Redundancy: 6.8 % / Rmerge(I) obs: 1.258 / Mean I/σ(I) obs: 1.1 / Num. unique obs: 3532 / CC1/2: 0.662 / % possible all: 97.6 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2→40 Å / Cor.coef. Fo:Fc: 0.943 / Cor.coef. Fo:Fc free: 0.935 / Rfactor Rfree error: 0 / SU R Cruickshank DPI: 0.166 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.17 / SU Rfree Blow DPI: 0.146 / SU Rfree Cruickshank DPI: 0.145
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Displacement parameters | Biso mean: 51.01 Å2
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Refine analyze | Luzzati coordinate error obs: 0.29 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: 1 / Resolution: 2→40 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2→2.05 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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