+Open data
-Basic information
Entry | Database: PDB / ID: 6fa2 | |||||||||||||||
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Title | Antibody derived (Abd-5) small molecule binding to KRAS. | |||||||||||||||
Components | (GTPase KRas) x 3 | |||||||||||||||
Keywords | ONCOPROTEIN / Abd-5 / inhibitor / KRAS | |||||||||||||||
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: 2.6 Å | |||||||||||||||
Authors | Quevedo, C.E. / Cruz-Migoni, A. / Ehebauer, M.T. / Carr, S.B. / Phillips, S.V.E. / Rabbitts, T.H. | |||||||||||||||
Funding support | United Kingdom, 4items
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Citation | Journal: Nat Commun / Year: 2018 Title: Small molecule inhibitors of RAS-effector protein interactions derived using an intracellular antibody fragment. Authors: Quevedo, C.E. / Cruz-Migoni, A. / Bery, N. / Miller, A. / Tanaka, T. / Petch, D. / Bataille, C.J.R. / Lee, L.Y.W. / Fallon, P.S. / Tulmin, H. / Ehebauer, M.T. / Fernandez-Fuentes, N. / ...Authors: Quevedo, C.E. / Cruz-Migoni, A. / Bery, N. / Miller, A. / Tanaka, T. / Petch, D. / Bataille, C.J.R. / Lee, L.Y.W. / Fallon, P.S. / Tulmin, H. / Ehebauer, M.T. / Fernandez-Fuentes, N. / Russell, A.J. / Carr, S.B. / Phillips, S.E.V. / Rabbitts, T.H. | |||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6fa2.cif.gz | 213.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6fa2.ent.gz | 178.3 KB | Display | PDB format |
PDBx/mmJSON format | 6fa2.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/fa/6fa2 ftp://data.pdbj.org/pub/pdb/validation_reports/fa/6fa2 | HTTPS FTP |
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-Related structure data
Related structure data | 5ocgC 5ocoC 5octC 6fa1C 6fa3C 6fa4C C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments:
NCS ensembles :
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-Components
-Protein , 3 types, 6 molecules ABDEFC
#1: Protein | Mass: 19023.482 Da / Num. of mol.: 1 / Mutation: Q61H 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 | ||
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#2: Protein | Mass: 19355.840 Da / Num. of mol.: 4 / Mutation: Q61H Source method: isolated from a genetically manipulated source Details: KRAS169 Q61H GppNHp / Source: (gene. exp.) Homo sapiens (human) / Gene: KRAS, KRAS2, RASK2 / Production host: Escherichia coli (E. coli) / References: UniProt: P01116 #3: Protein | | Mass: 19519.014 Da / Num. of mol.: 1 / Mutation: Q61H Source method: isolated from a genetically manipulated source Details: KRAS169 Q61H GppNHp / Source: (gene. exp.) Homo sapiens (human) / Gene: KRAS, KRAS2, RASK2 / Production host: Escherichia coli (E. coli) / Strain (production host): KRAS, KRAS2, RASK2 / References: UniProt: P01116 |
-Non-polymers , 4 types, 46 molecules
#4: Chemical | ChemComp-MG / #5: Chemical | ChemComp-GNP / #6: Chemical | ChemComp-D2W / #7: 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: 2.46 Å3/Da / Density % sol: 49.95 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 5.5 Details: 8-15% w/v Polyethylene glycol 3350 and 0.2M lithium citrate |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.9795 Å |
Detector | Type: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Sep 27, 2015 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9795 Å / Relative weight: 1 |
Reflection | Resolution: 2.6→93.81 Å / Num. obs: 36640 / % possible obs: 100 % / Redundancy: 7.4 % / CC1/2: 0.995 / Rmerge(I) obs: 0.058 / Rpim(I) all: 0.033 / Rrim(I) all: 0.067 / Net I/σ(I): 19.1 |
Reflection shell | Resolution: 2.6→2.72 Å / CC1/2: 0.748 / Rpim(I) all: 0.88 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.6→93.81 Å / Cor.coef. Fo:Fc: 0.953 / Cor.coef. Fo:Fc free: 0.944 / SU B: 14.101 / SU ML: 0.269 / Cross valid method: THROUGHOUT / ESU R: 1.023 / ESU R Free: 0.298 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 63.248 Å2
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Refinement step | Cycle: 1 / Resolution: 2.6→93.81 Å
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Refine LS restraints |
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