+Open data
-Basic information
Entry | Database: PDB / ID: 8fmk | |||||||||
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Title | Crystal structure of human KRAS with extended switch I loop | |||||||||
Components | GTPase KRas | |||||||||
Keywords | HYDROLASE / cancer | |||||||||
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 / Resolution: 1.48 Å | |||||||||
Authors | Brenner, R. / Landgraf, A. / Gonzalez-Gutierrez, G. / Bum-Erdene, K. / Meroueh, S.O. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Biochemistry / Year: 2023 Title: Crystal Packing Reveals a Potential Autoinhibited KRAS Dimer Interface and a Strategy for Small-Molecule Inhibition of RAS Signaling. Authors: Brenner, R.J. / Landgraf, A.D. / Bum-Erdene, K. / Gonzalez-Gutierrez, G. / Meroueh, S.O. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8fmk.cif.gz | 151.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8fmk.ent.gz | 97.8 KB | Display | PDB format |
PDBx/mmJSON format | 8fmk.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8fmk_validation.pdf.gz | 784 KB | Display | wwPDB validaton report |
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Full document | 8fmk_full_validation.pdf.gz | 784.6 KB | Display | |
Data in XML | 8fmk_validation.xml.gz | 11 KB | Display | |
Data in CIF | 8fmk_validation.cif.gz | 15.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/fm/8fmk ftp://data.pdbj.org/pub/pdb/validation_reports/fm/8fmk | HTTPS FTP |
-Related structure data
Related structure data | 8fmiC 8fmjC 5us4S S: Starting model for refinement 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
#1: Protein | Mass: 20273.811 Da / Num. of mol.: 1 / Mutation: C118S Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KRAS, KRAS2, RASK2 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P01116, small monomeric GTPase | ||||
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#2: Chemical | ChemComp-GDP / | ||||
#3: Chemical | ChemComp-MG / | ||||
#4: Chemical | #5: Water | ChemComp-HOH / | Has ligand of interest | N | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 1.78 Å3/Da / Density % sol: 30.95 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / Details: (NH)4Cl 0.2 M PEG3350 20-24% |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 4.2.2 / Wavelength: 1.00003 Å |
Detector | Type: RDI CMOS_8M / Detector: CMOS / Date: Nov 11, 2020 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.00003 Å / Relative weight: 1 |
Reflection | Resolution: 1.48→47.65 Å / Num. obs: 24873 / % possible obs: 99.7 % / Redundancy: 6.7 % / Biso Wilson estimate: 14.45 Å2 / CC1/2: 0.999 / Rpim(I) all: 0.028 / Rrim(I) all: 0.075 / Rsym value: 0.069 / Net I/σ(I): 18.5 |
Reflection shell | Resolution: 1.48→1.51 Å / Redundancy: 5.2 % / Mean I/σ(I) obs: 1.6 / Num. unique obs: 1155 / CC1/2: 0.668 / Rpim(I) all: 0.431 / Rrim(I) all: 1.012 / Rsym value: 0.91 / % possible all: 96 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5US4 Resolution: 1.48→42.12 Å / SU ML: 0.1647 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 24.8819 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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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 mean: 24.35 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.48→42.12 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group | Refine-ID: X-RAY DIFFRACTION / Auth asym-ID: A / Label asym-ID: A
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