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Yorodumi- PDB-7rt3: Crystal Structure of KRAS G12D with compound 24 (4-(4-[(1R,5S)-3,... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7rt3 | ||||||
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Title | Crystal Structure of KRAS G12D with compound 24 (4-(4-[(1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl]-8-fluoro-2-{[(2S,4S,7aR)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl]methoxy}pyrido[4,3-d]pyrimidin-7-yl)naphthalen-2-ol) bound | ||||||
Components | Isoform 2B of GTPase KRas | ||||||
Keywords | HYDROLASE/INHIBITOR / Oncoprotein / G12D / GTPase / KRAS / Oncology / KRAS4B / MRTX-1133 / HYDROLASE-INHIBITOR complex | ||||||
Function / homology | small monomeric GTPase / Ca2+ pathway / Chem-7NZ / GUANOSINE-5'-DIPHOSPHATE / Isoform 2B of GTPase KRas Function and homology information | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.56 Å | ||||||
Authors | Gunn, R.J. / Thomas, N.C. / Xiaolun, W. / Lawson, J.D. / Marx, M.A. | ||||||
Funding support | 1items
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Citation | Journal: J.Med.Chem. / Year: 2022 Title: Identification of MRTX1133, a Noncovalent, Potent, and Selective KRAS G12D Inhibitor. Authors: Wang, X. / Allen, S. / Blake, J.F. / Bowcut, V. / Briere, D.M. / Calinisan, A. / Dahlke, J.R. / Fell, J.B. / Fischer, J.P. / Gunn, R.J. / Hallin, J. / Laguer, J. / Lawson, J.D. / Medwid, J. ...Authors: Wang, X. / Allen, S. / Blake, J.F. / Bowcut, V. / Briere, D.M. / Calinisan, A. / Dahlke, J.R. / Fell, J.B. / Fischer, J.P. / Gunn, R.J. / Hallin, J. / Laguer, J. / Lawson, J.D. / Medwid, J. / Newhouse, B. / Nguyen, P. / O'Leary, J.M. / Olson, P. / Pajk, S. / Rahbaek, L. / Rodriguez, M. / Smith, C.R. / Tang, T.P. / Thomas, N.C. / Vanderpool, D. / Vigers, G.P. / Christensen, J.G. / Marx, M.A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7rt3.cif.gz | 99.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7rt3.ent.gz | 73.1 KB | Display | PDB format |
PDBx/mmJSON format | 7rt3.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7rt3_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 7rt3_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 7rt3_validation.xml.gz | 12.3 KB | Display | |
Data in CIF | 7rt3_validation.cif.gz | 18.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/rt/7rt3 ftp://data.pdbj.org/pub/pdb/validation_reports/rt/7rt3 | HTTPS FTP |
-Related structure data
Related structure data | 7rpzSC 7rt1C 7rt2C 7rt4C 7rt5C 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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Unit cell |
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-Components
#1: Protein | Mass: 19364.730 Da / Num. of mol.: 1 / Mutation: G12D, C51S, C80L, C118S Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KRAS, KRAS2, RASK2 / Production host: Escherichia coli (E. coli) / References: UniProt: P01116-2, small monomeric GTPase |
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#2: Chemical | ChemComp-GDP / |
#3: Chemical | ChemComp-7NZ / |
#4: Chemical | ChemComp-MG / |
#5: 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 | Density Matthews: 2.46 Å3/Da / Density % sol: 50.05 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion Details: 28% PEG8000, 100 mM sodium citrate, pH 4.6, 100 mM ammonium acetate |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 24-ID-E / Wavelength: 0.97918 Å |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jun 1, 2020 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97918 Å / Relative weight: 1 |
Reflection | Resolution: 1.56→50 Å / Num. obs: 28074 / % possible obs: 99.7 % / Redundancy: 3.2 % / CC1/2: 0.99 / Net I/σ(I): 16.1 |
Reflection shell | Resolution: 1.56→1.58 Å / Mean I/σ(I) obs: 3.6 / Num. unique obs: 1277 / CC1/2: 0.97 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB entry 7RPZ Resolution: 1.56→32.13 Å / SU ML: 0.15 / Cross valid method: THROUGHOUT / σ(F): 1.38 / Phase error: 19.2 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 72.97 Å2 / Biso mean: 21.5202 Å2 / Biso min: 7.89 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.56→32.13 Å
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 10
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Refinement TLS params. | Method: refined / Origin x: -2.0254 Å / Origin y: -2.2137 Å / Origin z: -12.9465 Å
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Refinement TLS group |
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