+Open data
-Basic information
Entry | Database: PDB / ID: 7pcd | ||||||
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Title | HER2 IN COMPLEX WITH A COVALENT INHIBITOR | ||||||
Components | Receptor tyrosine-protein kinase erbB-2 | ||||||
Keywords | TRANSFERASE / HER2 / covalent Inhibitor | ||||||
Function / homology | Function and homology information negative regulation of immature T cell proliferation in thymus / ERBB3:ERBB2 complex / ERBB2-ERBB4 signaling pathway / GRB7 events in ERBB2 signaling / immature T cell proliferation in thymus / RNA polymerase I core binding / regulation of microtubule-based process / ErbB-3 class receptor binding / semaphorin receptor complex / Sema4D induced cell migration and growth-cone collapse ...negative regulation of immature T cell proliferation in thymus / ERBB3:ERBB2 complex / ERBB2-ERBB4 signaling pathway / GRB7 events in ERBB2 signaling / immature T cell proliferation in thymus / RNA polymerase I core binding / regulation of microtubule-based process / ErbB-3 class receptor binding / semaphorin receptor complex / Sema4D induced cell migration and growth-cone collapse / motor neuron axon guidance / neurotransmitter receptor localization to postsynaptic specialization membrane / PLCG1 events in ERBB2 signaling / ERBB2-EGFR signaling pathway / neuromuscular junction development / positive regulation of Rho protein signal transduction / ERBB2 Activates PTK6 Signaling / Drug-mediated inhibition of ERBB2 signaling / Resistance of ERBB2 KD mutants to trastuzumab / Resistance of ERBB2 KD mutants to sapitinib / Resistance of ERBB2 KD mutants to tesevatinib / Resistance of ERBB2 KD mutants to neratinib / Resistance of ERBB2 KD mutants to osimertinib / Resistance of ERBB2 KD mutants to afatinib / Resistance of ERBB2 KD mutants to AEE788 / Resistance of ERBB2 KD mutants to lapatinib / Drug resistance in ERBB2 TMD/JMD mutants / enzyme-linked receptor protein signaling pathway / positive regulation of transcription by RNA polymerase I / ERBB2-ERBB3 signaling pathway / oligodendrocyte differentiation / ERBB2 Regulates Cell Motility / semaphorin-plexin signaling pathway / PI3K events in ERBB2 signaling / positive regulation of cell adhesion / positive regulation of protein targeting to membrane / regulation of angiogenesis / coreceptor activity / Schwann cell development / Signaling by ERBB2 / cellular response to epidermal growth factor stimulus / myelination / Downregulation of ERBB2:ERBB3 signaling / GRB2 events in ERBB2 signaling / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / transmembrane receptor protein tyrosine kinase activity / SHC1 events in ERBB2 signaling / Constitutive Signaling by Overexpressed ERBB2 / neurogenesis / basal plasma membrane / regulation of ERK1 and ERK2 cascade / phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of translation / positive regulation of epithelial cell proliferation / cell surface receptor protein tyrosine kinase signaling pathway / Signaling by ERBB2 TMD/JMD mutants / positive regulation of MAP kinase activity / wound healing / neuromuscular junction / Signaling by ERBB2 ECD mutants / neuron differentiation / Signaling by ERBB2 KD Mutants / receptor protein-tyrosine kinase / receptor tyrosine kinase binding / cellular response to growth factor stimulus / Downregulation of ERBB2 signaling / ruffle membrane / peptidyl-tyrosine phosphorylation / Constitutive Signaling by Aberrant PI3K in Cancer / transmembrane signaling receptor activity / PIP3 activates AKT signaling / myelin sheath / presynaptic membrane / heart development / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / RAF/MAP kinase cascade / positive regulation of cell growth / basolateral plasma membrane / protein tyrosine kinase activity / positive regulation of MAPK cascade / early endosome / cell surface receptor signaling pathway / receptor complex / endosome membrane / intracellular signal transduction / apical plasma membrane / positive regulation of protein phosphorylation / protein heterodimerization activity / protein phosphorylation / signaling receptor binding / positive regulation of cell population proliferation / negative regulation of apoptotic process / perinuclear region of cytoplasm / signal transduction / nucleoplasm / ATP binding / membrane / identical protein binding / nucleus / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.77 Å | ||||||
Authors | Bader, G. | ||||||
Funding support | Austria, 1items
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Citation | Journal: Nat Cancer / Year: 2022 Title: Discovery of potent and selective HER2 inhibitors with efficacy against HER2 exon 20 insertion-driven tumors, which preserve wild-type EGFR signaling. Authors: Wilding, B. / Scharn, D. / Bose, D. / Baum, A. / Santoro, V. / Chetta, P. / Schnitzer, R. / Botesteanu, D.A. / Reiser, C. / Kornigg, S. / Knesl, P. / Hormann, A. / Koferle, A. / Corcokovic, ...Authors: Wilding, B. / Scharn, D. / Bose, D. / Baum, A. / Santoro, V. / Chetta, P. / Schnitzer, R. / Botesteanu, D.A. / Reiser, C. / Kornigg, S. / Knesl, P. / Hormann, A. / Koferle, A. / Corcokovic, M. / Lieb, S. / Scholz, G. / Bruchhaus, J. / Spina, M. / Balla, J. / Peric-Simov, B. / Zimmer, J. / Mitzner, S. / Fett, T.N. / Beran, A. / Lamarre, L. / Gerstberger, T. / Gerlach, D. / Bauer, M. / Bergner, A. / Schlattl, A. / Bader, G. / Treu, M. / Engelhardt, H. / Zahn, S. / Fuchs, J.E. / Zuber, J. / Ettmayer, P. / Pearson, M. / Petronczki, M. / Kraut, N. / McConnell, D.B. / Solca, F. / Neumuller, R.A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7pcd.cif.gz | 75.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7pcd.ent.gz | 52.8 KB | Display | PDB format |
PDBx/mmJSON format | 7pcd.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/pc/7pcd ftp://data.pdbj.org/pub/pdb/validation_reports/pc/7pcd | HTTPS FTP |
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-Related structure data
Related structure data | 3rcdS 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
#1: Protein | Mass: 36968.629 Da / Num. of mol.: 1 / Fragment: NONE Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ERBB2, HER2, MLN19, NEU, NGL / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: P04626, receptor protein-tyrosine kinase |
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#2: Chemical | ChemComp-70I / |
#3: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.03 Å3/Da / Density % sol: 39.56 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion / pH: 6.75 Details: 18% PEG3350, 50mM ammonium tartrate, 150mM sodium tartrate and 100mM BIS-TRIS |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: CLSI / Beamline: 08ID-1 / Wavelength: 0.97949 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Oct 2, 2019 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97949 Å / Relative weight: 1 |
Reflection | Resolution: 1.77→61.19 Å / Num. obs: 24847 / % possible obs: 95.4 % / Redundancy: 5.1 % / Biso Wilson estimate: 37.966 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.064 / Rrim(I) all: 0.071 / Χ2: 1.144 / Net I/σ(I): 10.65 |
Reflection shell | Resolution: 1.77→2.02 Å / Redundancy: 5.1 % / Rmerge(I) obs: 0.438 / Mean I/σ(I) obs: 3.19 / Num. unique obs: 90 / CC1/2: 0.999 / Rrim(I) all: 0.038 / % possible all: 97.6 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3RCD Resolution: 1.77→61.19 Å / Cor.coef. Fo:Fc: 0.966 / Cor.coef. Fo:Fc free: 0.955 / SU B: 5.201 / SU ML: 0.144 / SU R Cruickshank DPI: 0.1615 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.161 / ESU R Free: 0.144 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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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: 111.05 Å2 / Biso mean: 40.971 Å2 / Biso min: 23.9 Å2
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Refinement step | Cycle: final / Resolution: 1.77→61.19 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.77→1.816 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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