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Yorodumi- PDB-7rov: KRAS G12D Mutant in complex with GMPPCP and cyclic peptide MP-9903 -
+Open data
-Basic information
Entry | Database: PDB / ID: 7rov | |||||||||
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Title | KRAS G12D Mutant in complex with GMPPCP and cyclic peptide MP-9903 | |||||||||
Components |
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Keywords | HYDROLASE / KRAS / cyclic peptide / non-natural amino acid | |||||||||
Function / homology | Function and homology information forebrain astrocyte development / negative regulation of epithelial cell differentiation / regulation of synaptic transmission, GABAergic / 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 / negative regulation of epithelial cell differentiation / regulation of synaptic transmission, GABAergic / 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 / Signaling by FGFR4 in disease / SHC-mediated cascade:FGFR1 / Erythropoietin activates RAS / protein-membrane adaptor activity / FRS-mediated FGFR3 signaling / Signaling by CSF3 (G-CSF) / positive regulation of glial cell proliferation / Signaling by FLT3 ITD and TKD mutants / homeostasis of number of cells within a tissue / FRS-mediated FGFR2 signaling / FRS-mediated FGFR4 signaling / Signaling by FGFR3 in disease / FRS-mediated FGFR1 signaling / p38MAPK events / Tie2 Signaling / Signaling by FGFR2 in disease / striated muscle cell differentiation / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / EGFR Transactivation by Gastrin / Signaling by FLT3 fusion proteins / FLT3 Signaling / Signaling by FGFR1 in disease / Ras activation upon Ca2+ influx through NMDA receptor / GRB2 events in ERBB2 signaling / NCAM signaling for neurite out-growth / CD209 (DC-SIGN) signaling / SHC1 events in ERBB2 signaling / Downstream signal transduction / Constitutive Signaling by Overexpressed ERBB2 / Insulin receptor signalling cascade / small monomeric GTPase / G protein activity / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / VEGFR2 mediated cell proliferation / FCERI mediated MAPK activation / Signaling by ERBB2 TMD/JMD mutants / regulation of long-term neuronal synaptic plasticity / 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 / Signaling by RAF1 mutants / GDP binding / 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 / DAP12 signaling / Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants / Ca2+ pathway / gene expression / actin cytoskeleton organization / RAF/MAP kinase cascade / neuron apoptotic process / mitochondrial outer membrane / negative regulation of neuron apoptotic process / Ras protein signal transduction / positive regulation of protein phosphorylation / Golgi membrane / focal adhesion Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) synthetic construct (others) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.32 Å | |||||||||
Authors | Orth, P. | |||||||||
Funding support | 1items
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Citation | Journal: Chem Sci / Year: 2021 Title: Discovery of cell active macrocyclic peptides with on-target inhibition of KRAS signaling. Authors: Lim, S. / Boyer, N. / Boo, N. / Huang, C. / Venkatachalam, G. / Angela Juang, Y.C. / Garrigou, M. / Kaan, H.Y.K. / Duggal, R. / Peh, K.M. / Sadruddin, A. / Gopal, P. / Yuen, T.Y. / Ng, S. / ...Authors: Lim, S. / Boyer, N. / Boo, N. / Huang, C. / Venkatachalam, G. / Angela Juang, Y.C. / Garrigou, M. / Kaan, H.Y.K. / Duggal, R. / Peh, K.M. / Sadruddin, A. / Gopal, P. / Yuen, T.Y. / Ng, S. / Kannan, S. / Brown, C.J. / Verma, C.S. / Orth, P. / Peier, A. / Ge, L. / Yu, X. / Bhatt, B. / Chen, F. / Wang, E. / Li, N.J. / Gonzales, R.J. / Stoeck, A. / Henry, B. / Sawyer, T.K. / Lane, D.P. / Johannes, C.W. / Biswas, K. / Partridge, A.W. #1: Journal: Biorxiv / Year: 2021 Title: Discovery of cell active macrocyclic peptides with on-target inhibition of KRAS signaling Authors: Lim, S. / Boyer, N. / Boo, N. / Huang, C. / Venkatachalam, G. / Juang, Y.C.A. / Garrigou, M. / Kaan, K. / Peh, K.M. / Sadruddin, A. / Gopal, P. / Duggal, R. / Yuen, T.Y. / Ng, S. / Kannan, S. ...Authors: Lim, S. / Boyer, N. / Boo, N. / Huang, C. / Venkatachalam, G. / Juang, Y.C.A. / Garrigou, M. / Kaan, K. / Peh, K.M. / Sadruddin, A. / Gopal, P. / Duggal, R. / Yuen, T.Y. / Ng, S. / Kannan, S. / Brown, C.J. / Verma, C. / Orth, P. / Peier, A. / Ge, L. / Yu, X. / Bhatt, B. / Chen, F. / Wang, E. / Li, N.J. / Gonzalez, R. / Stoeck, A. / Henry, B. / Sawyer, T.K. / Lane, D.P. / Johannes, C.W. / Biswas, K. / Partridge, A.W. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7rov.cif.gz | 97.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7rov.ent.gz | 70.8 KB | Display | PDB format |
PDBx/mmJSON format | 7rov.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ro/7rov ftp://data.pdbj.org/pub/pdb/validation_reports/ro/7rov | HTTPS FTP |
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-Related structure data
Related structure data | 5xcoS S: Starting model for refinement |
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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
-Protein / Protein/peptide , 2 types, 4 molecules ABEF
#1: Protein | Mass: 21588.719 Da / Num. of mol.: 2 / Mutation: G12D 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 #2: Protein/peptide | Type: Oligopeptide / Class: Substrate analog / Mass: 1585.866 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) / References: BIRD: PRD_002482 |
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-Non-polymers , 4 types, 312 molecules
#3: Chemical | #4: Chemical | #5: Chemical | ChemComp-GOL / | #6: Water | ChemComp-HOH / | |
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-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: 1.93 Å3/Da / Density % sol: 36.3 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, sitting drop / pH: 6.5 / Details: 100mM Bis-Tris and 25% PEG 4000 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Mar 16, 2018 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.32→47.9 Å / Num. obs: 74611 / % possible obs: 96.2 % / Redundancy: 3.3 % / CC1/2: 0.996 / Net I/σ(I): 9.7 |
Reflection shell | Resolution: 1.32→1.356 Å / Num. unique obs: 3731 / CC1/2: 0.55 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5xco Resolution: 1.32→47.94 Å / Cor.coef. Fo:Fc: 0.954 / Cor.coef. Fo:Fc free: 0.95 / SU R Cruickshank DPI: 0.061 / Cross valid method: THROUGHOUT / SU R Blow DPI: 0.062 / SU Rfree Blow DPI: 0.062 / SU Rfree Cruickshank DPI: 0.061
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Displacement parameters | Biso mean: 19.76 Å2
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Refine analyze | Luzzati coordinate error obs: 0.18 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.32→47.94 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.32→1.33 Å
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