+Open data
-Basic information
Entry | Database: PDB / ID: 6yxw | ||||||
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Title | Affimer K3 - KRAS protein complex | ||||||
Components |
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Keywords | PROTEIN BINDING / Protein complex / Affimer / KRAS / Inhibitor | ||||||
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 / molecular replacement / Resolution: 2.06 Å | ||||||
Authors | Trinh, C.H. / Haza, K.Z. / Rao, A. / Martin, H.L. / Tiede, C. / Edwards, T.A. / McPherson, M.J. / Tomlinson, D.C. | ||||||
Funding support | United Kingdom, 1items
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Citation | Journal: Nat Commun / Year: 2021 Title: RAS-inhibiting biologics identify and probe druggable pockets including an SII-alpha 3 allosteric site. Authors: Haza, K.Z. / Martin, H.L. / Rao, A. / Turner, A.L. / Saunders, S.E. / Petersen, B. / Tiede, C. / Tipping, K. / Tang, A.A. / Ajayi, M. / Taylor, T. / Harvey, M. / Fishwick, K.M. / Adams, T.L. ...Authors: Haza, K.Z. / Martin, H.L. / Rao, A. / Turner, A.L. / Saunders, S.E. / Petersen, B. / Tiede, C. / Tipping, K. / Tang, A.A. / Ajayi, M. / Taylor, T. / Harvey, M. / Fishwick, K.M. / Adams, T.L. / Gaule, T.G. / Trinh, C.H. / Johnson, M. / Breeze, A.L. / Edwards, T.A. / McPherson, M.J. / Tomlinson, D.C. #1: Journal: Biorxiv / Year: 2020 Title: RAS-inhibiting biologics identify and probe druggable pockets including an SII-alpha3 allosteric site Authors: Haza, K.Z. / Martin, H.L. / Rao, A. / Turner, A. / Saunders, S.E. / Petersen, B. / Tiede, C. / Tipping, K. / Ajayi, M. / Fishwick, K.M. / Adams, T.L. / Trinh, C.H. / Breeze, A.L. / Edwards, ...Authors: Haza, K.Z. / Martin, H.L. / Rao, A. / Turner, A. / Saunders, S.E. / Petersen, B. / Tiede, C. / Tipping, K. / Ajayi, M. / Fishwick, K.M. / Adams, T.L. / Trinh, C.H. / Breeze, A.L. / Edwards, T.A. / McPherson, M.J. / Tomlinson, D.C. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6yxw.cif.gz | 226.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6yxw.ent.gz | 180.1 KB | Display | PDB format |
PDBx/mmJSON format | 6yxw.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/yx/6yxw ftp://data.pdbj.org/pub/pdb/validation_reports/yx/6yxw | HTTPS FTP |
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-Related structure data
Related structure data | 6yr8C 7ny8C 4n6tS 4obeS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 19295.742 Da / Num. of mol.: 2 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 #2: Protein | Mass: 12537.210 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli) #3: Chemical | #4: Chemical | #5: Water | ChemComp-HOH / | Has ligand of interest | N | |
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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: 2.47 Å3/Da / Density % sol: 50.21 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, sitting drop / pH: 5.6 Details: 2M ammonium sulfate, 0.2M potassium sodium tartrate, 0.1M tri-sodium citrate |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: MASSIF-1 / Wavelength: 0.966 Å |
Detector | Type: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Jul 27, 2018 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.966 Å / Relative weight: 1 |
Reflection | Resolution: 2.06→54.16 Å / Num. obs: 38740 / % possible obs: 99.7 % / Redundancy: 2.9 % / CC1/2: 0.978 / Rmerge(I) obs: 0.089 / Rpim(I) all: 0.063 / Net I/σ(I): 6.2 |
Reflection shell | Resolution: 2.06→2.11 Å / Redundancy: 3 % / Rmerge(I) obs: 0.393 / Num. unique obs: 2830 / CC1/2: 0.961 / Rpim(I) all: 0.465 / % possible all: 99.9 |
-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4OBE, 4N6T Resolution: 2.06→54.16 Å / Cor.coef. Fo:Fc: 0.939 / Cor.coef. Fo:Fc free: 0.896 / SU B: 17.861 / SU ML: 0.216 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.233 / ESU R Free: 0.199 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 112.18 Å2 / Biso mean: 44.644 Å2 / Biso min: 22.84 Å2
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Refinement step | Cycle: final / Resolution: 2.06→54.16 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.06→2.113 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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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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