+Open data
-Basic information
Entry | Database: PDB / ID: 6h46 | ||||||
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Title | Human KRAS in complex with darpin K13 | ||||||
Components |
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Keywords | SIGNALING PROTEIN / GTP-ASE / darpin / KRAS signalling | ||||||
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: 2.22 Å | ||||||
Authors | Debreczeni, J.E. / Bery, N. / Legg, S. / Breed, J. / Embrey, K. / Stubbs, C. / Kolasinska-Zwierz, P. / Barrett, N. / Marwood, R. / Watson, J. ...Debreczeni, J.E. / Bery, N. / Legg, S. / Breed, J. / Embrey, K. / Stubbs, C. / Kolasinska-Zwierz, P. / Barrett, N. / Marwood, R. / Watson, J. / Tart, J. / Overman, R. / Miller, A. / Phillips, C. / Minter, R. / Rabbitts, T.H. | ||||||
Citation | Journal: Nat Commun / Year: 2019 Title: KRAS-specific inhibition using a DARPin binding to a site in the allosteric lobe. Authors: Bery, N. / Legg, S. / Debreczeni, J. / Breed, J. / Embrey, K. / Stubbs, C. / Kolasinska-Zwierz, P. / Barrett, N. / Marwood, R. / Watson, J. / Tart, J. / Overman, R. / Miller, A. / Phillips, ...Authors: Bery, N. / Legg, S. / Debreczeni, J. / Breed, J. / Embrey, K. / Stubbs, C. / Kolasinska-Zwierz, P. / Barrett, N. / Marwood, R. / Watson, J. / Tart, J. / Overman, R. / Miller, A. / Phillips, C. / Minter, R. / 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 | 6h46.cif.gz | 142.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6h46.ent.gz | 116.8 KB | Display | PDB format |
PDBx/mmJSON format | 6h46.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/h4/6h46 ftp://data.pdbj.org/pub/pdb/validation_reports/h4/6h46 | HTTPS FTP |
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-Related 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: 19208.643 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KRAS, KRAS2, RASK2 / Production host: Escherichia coli BL21 (bacteria) / References: UniProt: P01116 | ||
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#2: Protein | Mass: 16832.055 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli BL21 (bacteria) | ||
#3: Chemical | ChemComp-GDP / | ||
#4: Chemical | #5: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.84 Å3/Da / Density % sol: 56.62 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop Details: 0.5-1.0M lithium sulfate 0.5-1.0M ammonium sulfate 100mM tri-sodium citrate pH5.5 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I04-1 / Wavelength: 0.976 Å |
Detector | Type: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: May 21, 2014 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.976 Å / Relative weight: 1 |
Reflection | Resolution: 2.22→51.5 Å / Num. obs: 21240 / % possible obs: 99.9 % / Redundancy: 13.1 % / CC1/2: 0.999 / Rmerge(I) obs: 0.096 / Rpim(I) all: 0.039 / Net I/σ(I): 20.9 |
Reflection shell | Resolution: 2.22→2.28 Å / Redundancy: 12.1 % / Rmerge(I) obs: 0.653 / Mean I/σ(I) obs: 0.885 / Num. unique obs: 1532 / CC1/2: 0.885 / Rpim(I) all: 0.277 / % possible all: 99.2 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.22→23.59 Å / Cor.coef. Fo:Fc: 0.951 / Cor.coef. Fo:Fc free: 0.917 / SU B: 9.646 / SU ML: 0.134 / Cross valid method: THROUGHOUT / ESU R: 0.231 / ESU R Free: 0.194 / 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: 34.531 Å2
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Refinement step | Cycle: 1 / Resolution: 2.22→23.59 Å
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