+Open data
-Basic information
Entry | Database: PDB / ID: 8ezg | |||||||||||||||||||||
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Title | Monobody 12D1 bound to KRAS(G12D) | |||||||||||||||||||||
Components |
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Keywords | SIGNALING PROTEIN/DE NOVO PROTEIN / SIGNALING PROTEIN-DE NOVO PROTEIN complex | |||||||||||||||||||||
Function / homology | Function and homology information forebrain astrocyte development / regulation of synaptic transmission, GABAergic / negative regulation of epithelial cell differentiation / 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 / Signaling by RAS GAP mutants / Signaling by RAS GTPase mutants ...forebrain astrocyte development / regulation of synaptic transmission, GABAergic / negative regulation of epithelial cell differentiation / 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 / Signaling by RAS GAP mutants / Signaling by RAS GTPase mutants / Activation of RAS in B cells / 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 / Signalling to RAS / glial cell proliferation / SHC-related events triggered by IGF1R / Activated NTRK2 signals through FRS2 and FRS3 / Estrogen-stimulated signaling through PRKCZ / SHC-mediated cascade:FGFR3 / MET activates RAS signaling / PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases / Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants / Signaling by PDGFRA extracellular domain mutants / SHC-mediated cascade:FGFR2 / SHC-mediated cascade:FGFR4 / protein-membrane adaptor activity / Signaling by FGFR4 in disease / SHC-mediated cascade:FGFR1 / Erythropoietin activates RAS / homeostasis of number of cells within a tissue / positive regulation of glial cell proliferation / FRS-mediated FGFR3 signaling / Signaling by CSF3 (G-CSF) / Signaling by FLT3 ITD and TKD mutants / FRS-mediated FGFR2 signaling / FRS-mediated FGFR4 signaling / Signaling by FGFR3 in disease / p38MAPK events / FRS-mediated FGFR1 signaling / Tie2 Signaling / Signaling by FGFR2 in disease / GRB2 events in EGFR signaling / striated muscle cell differentiation / SHC1 events in EGFR signaling / EGFR Transactivation by Gastrin / Signaling by FLT3 fusion proteins / Ras activation upon Ca2+ influx through NMDA receptor / FLT3 Signaling / Signaling by FGFR1 in disease / GRB2 events in ERBB2 signaling / NCAM signaling for neurite out-growth / CD209 (DC-SIGN) signaling / SHC1 events in ERBB2 signaling / Downstream signal transduction / Insulin receptor signalling cascade / Constitutive Signaling by Overexpressed ERBB2 / small monomeric GTPase / G protein activity / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / VEGFR2 mediated cell proliferation / FCERI mediated MAPK activation / regulation of long-term neuronal synaptic plasticity / Signaling by ERBB2 TMD/JMD mutants / RAF activation / Signaling by high-kinase activity BRAF mutants / Constitutive Signaling by EGFRvIII / visual learning / MAP2K and MAPK activation / Signaling by ERBB2 ECD mutants / Signaling by ERBB2 KD Mutants / Signaling by SCF-KIT / cytoplasmic side of plasma membrane / Regulation of RAS by GAPs / Negative regulation of MAPK pathway / RAS processing / GDP binding / 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 / Signaling by CSF1 (M-CSF) in myeloid cells / MAPK cascade / Signaling by BRAF and RAF1 fusions / Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants / DAP12 signaling / Ca2+ pathway / gene expression / actin cytoskeleton organization / RAF/MAP kinase cascade / neuron apoptotic process / Ras protein signal transduction / 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: 2.52 Å | |||||||||||||||||||||
Authors | Hattori, T. / Glasser, E. / Akkapeddi, P. / Ketavarapu, G. / Teng, K.W. / Koide, A. / Koide, S. | |||||||||||||||||||||
Funding support | United States, 6items
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Citation | Journal: Proc.Natl.Acad.Sci.USA / Year: 2023 Title: Exploring switch II pocket conformation of KRAS(G12D) with mutant-selective monobody inhibitors. Authors: Akkapeddi, P. / Hattori, T. / Khan, I. / Glasser, E. / Koide, A. / Ketavarapu, G. / Whaby, M. / Zuberi, M. / Teng, K.W. / Lefler, J. / Maso, L. / Bang, I. / Ostrowski, M.C. / O'Bryan, J.P. / Koide, S. | |||||||||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8ezg.cif.gz | 71.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8ezg.ent.gz | 50.3 KB | Display | PDB format |
PDBx/mmJSON format | 8ezg.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ez/8ezg ftp://data.pdbj.org/pub/pdb/validation_reports/ez/8ezg | HTTPS FTP |
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-Related structure data
Related structure data | 8f0mC 5vpzS 7l0gS C: citing same article (ref.) S: Starting model for refinement |
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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 on special symmetry positions |
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-Components
-Protein / Antibody , 2 types, 2 molecules AB
#1: Protein | Mass: 19178.498 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, small monomeric GTPase |
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#2: Antibody | Mass: 9710.778 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli) |
-Non-polymers , 4 types, 129 molecules
#3: Chemical | ChemComp-GDP / |
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#4: Chemical | ChemComp-MG / |
#5: Chemical | ChemComp-NA / |
#6: Water | ChemComp-HOH / |
-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: 3.96 Å3/Da / Density % sol: 68.94 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, sitting drop / pH: 7 / Details: 2.8 M sodium acetate trihydrate |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.97918 Å |
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Sep 24, 2022 |
Radiation | Monochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97918 Å / Relative weight: 1 |
Reflection | Resolution: 2.52→50 Å / Num. obs: 16221 / % possible obs: 99.9 % / Redundancy: 8.7 % / CC1/2: 0.986 / CC star: 0.996 / Rmerge(I) obs: 0.092 / Rpim(I) all: 0.033 / Rrim(I) all: 0.098 / Χ2: 1.09 / Net I/σ(I): 20.3 |
Reflection shell | Resolution: 2.52→2.56 Å / Redundancy: 9 % / Rmerge(I) obs: 0.324 / Mean I/σ(I) obs: 7.4 / Num. unique obs: 798 / CC1/2: 0.973 / CC star: 0.993 / Rpim(I) all: 0.113 / Rrim(I) all: 0.344 / Χ2: 1.099 / % possible all: 99.9 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB entries 7L0G & 5VPZ Resolution: 2.52→45.17 Å / SU ML: 0.26 / Cross valid method: THROUGHOUT / σ(F): 1.37 / Phase error: 20.76 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.52→45.17 Å
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Refine LS restraints |
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LS refinement shell |
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