+Open data
-Basic information
Entry | Database: PDB / ID: 4l8g | ||||||
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Title | Crystal Structure of K-Ras G12C, GDP-bound | ||||||
Components | GTPase KRas | ||||||
Keywords | SIGNALING PROTEIN / GTPase / activating mutant | ||||||
Function / homology | Function and homology information forebrain astrocyte development / negative regulation of epithelial cell differentiation / regulation of synaptic transmission, GABAergic / type I pneumocyte differentiation / epithelial tube branching involved in lung morphogenesis / Rac protein signal transduction / skeletal muscle cell differentiation / positive regulation of Rac protein signal transduction / Signaling by RAS GAP mutants / Signaling by RAS GTPase mutants ...forebrain astrocyte development / negative regulation of epithelial cell differentiation / regulation of synaptic transmission, GABAergic / type I pneumocyte differentiation / epithelial tube branching involved in lung morphogenesis / Rac protein signal transduction / skeletal muscle cell differentiation / positive regulation of Rac protein signal transduction / Signaling by RAS GAP mutants / Signaling by RAS GTPase mutants / Activation of RAS in B cells / positive regulation of glial cell proliferation / RAS signaling downstream of NF1 loss-of-function variants / RUNX3 regulates p14-ARF / SOS-mediated signalling / Activated NTRK3 signals through RAS / Activated NTRK2 signals through RAS / SHC1 events in ERBB4 signaling / GRB2 events in EGFR signaling / EGFR Transactivation by Gastrin / SHC1 events in EGFR signaling / Signalling to RAS / GRB2 events in ERBB2 signaling / SHC-related events triggered by IGF1R / Activated NTRK2 signals through FRS2 and FRS3 / glial cell proliferation / Estrogen-stimulated signaling through PRKCZ / SHC1 events in ERBB2 signaling / SHC-mediated cascade:FGFR3 / MET activates RAS signaling / Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants / Signaling by PDGFRA extracellular domain mutants / SHC-mediated cascade:FGFR2 / PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases / SHC-mediated cascade:FGFR4 / Signaling by FGFR4 in disease / Erythropoietin activates RAS / SHC-mediated cascade:FGFR1 / protein-membrane adaptor activity / FRS-mediated FGFR3 signaling / Signaling by CSF3 (G-CSF) / Signaling by FLT3 ITD and TKD mutants / homeostasis of number of cells within a tissue / FRS-mediated FGFR2 signaling / Signaling by FGFR3 in disease / FRS-mediated FGFR4 signaling / p38MAPK events / Tie2 Signaling / FRS-mediated FGFR1 signaling / striated muscle cell differentiation / Signaling by FGFR2 in disease / Signaling by FLT3 fusion proteins / FLT3 Signaling / Ras activation upon Ca2+ influx through NMDA receptor / Signaling by FGFR1 in disease / CD209 (DC-SIGN) signaling / NCAM signaling for neurite out-growth / Downstream signal transduction / Constitutive Signaling by Overexpressed ERBB2 / Insulin receptor signalling cascade / Signaling by ERBB2 TMD/JMD mutants / small monomeric GTPase / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / G protein activity / VEGFR2 mediated cell proliferation / Constitutive Signaling by EGFRvIII / Signaling by ERBB2 ECD mutants / Signaling by ERBB2 KD Mutants / FCERI mediated MAPK activation / RAF activation / regulation of long-term neuronal synaptic plasticity / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation / visual learning / Signaling by SCF-KIT / cytoplasmic side of plasma membrane / Regulation of RAS by GAPs / RAS processing / Negative regulation of MAPK pathway / Signaling by CSF1 (M-CSF) in myeloid cells / Signaling by RAF1 mutants / Signaling by moderate kinase activity BRAF mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants / GDP binding / MAPK cascade / Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants / Signaling by BRAF and RAF1 fusions / DAP12 signaling / Ca2+ pathway / RAF/MAP kinase cascade / gene expression / actin cytoskeleton organization / Ras protein signal transduction / neuron apoptotic process / negative regulation of neuron apoptotic process / mitochondrial outer membrane / positive regulation of protein phosphorylation / Golgi membrane / focal adhesion Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.521 Å | ||||||
Authors | Ostrem, J.M. / Peters, U. / Sos, M.L. / Wells, J.A. / Shokat, K.M. | ||||||
Citation | Journal: Nature / Year: 2013 Title: K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Authors: Ostrem, J.M. / Peters, U. / Sos, M.L. / Wells, J.A. / Shokat, K.M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4l8g.cif.gz | 111.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4l8g.ent.gz | 86.6 KB | Display | PDB format |
PDBx/mmJSON format | 4l8g.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4l8g_validation.pdf.gz | 787 KB | Display | wwPDB validaton report |
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Full document | 4l8g_full_validation.pdf.gz | 788.1 KB | Display | |
Data in XML | 4l8g_validation.xml.gz | 9.8 KB | Display | |
Data in CIF | 4l8g_validation.cif.gz | 13.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/l8/4l8g ftp://data.pdbj.org/pub/pdb/validation_reports/l8/4l8g | HTTPS FTP |
-Related structure data
Related structure data | 4l9sC 4l9wC 4lpkC 4lrwC 4lucC 4lv6C 4lyfC 4lyhC 4lyjC 4m1oC 4m1sC 4m1tC 4m1wC 4m1yC 4m21C 4m22C 3gftS C: citing same article (ref.) S: Starting model for refinement |
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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 on special symmetry positions |
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-Components
#1: Protein | Mass: 19374.902 Da / Num. of mol.: 1 / Fragment: UNP residues 1-169 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KRAS, KRAS isoform 2B, KRAS2, RASK2 / Plasmid: pJexpress411 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P01116 |
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#2: Chemical | ChemComp-GDP / |
#3: Chemical | ChemComp-MG / |
#4: Chemical | ChemComp-NA / |
#5: Water | ChemComp-HOH / |
Sequence details | THE SEQUENCE IN THE STRUCTURE REPRESENTS ISOFORM 2B OF GTPASE KRAS. THIS ISOFORM DIFFERS FROM THE ...THE SEQUENCE IN THE STRUCTURE REPRESENTS |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 1.99 Å3/Da / Density % sol: 38.08 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7.5 Details: 21% PEG3350, 0.2M CaCl2, pH 7.5, VAPOR DIFFUSION, HANGING DROP, temperature 293K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 8.2.2 / Wavelength: 0.9999 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Apr 25, 2010 |
Diffraction measurement | Details: 1.00 degrees, 10.0 sec, detector distance 200.15 mm Method: \w scans |
Radiation | Monochromator: Double crystal, Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9999 Å / Relative weight: 1 |
Reflection | Av R equivalents: 0.042 / Number: 156693 |
Reflection | Resolution: 1.52→20 Å / Num. obs: 23541 / % possible obs: 99.9 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 6.7 % / Rmerge(I) obs: 0.042 / Rsym value: 0.042 / Net I/σ(I): 38.873 |
Reflection shell | Resolution: 1.52→1.55 Å / Redundancy: 6.2 % / Rmerge(I) obs: 0.349 / Mean I/σ(I) obs: 5 / Rsym value: 0.349 / % possible all: 100 |
Cell measurement | Reflection used: 156693 |
-Phasing
Phasing | Method: molecular replacement | |||||||||
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Phasing MR |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 3GFT Resolution: 1.521→19.731 Å / Occupancy max: 1 / Occupancy min: 0.31 / FOM work R set: 0.8902 / SU ML: 0.13 / σ(F): 1.36 / Phase error: 17.73 / 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: 94.89 Å2 / Biso mean: 31.8471 Å2 / Biso min: 12.72 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.521→19.731 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 14
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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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