[English] 日本語
Yorodumi
- PDB-4r5s: Crystal structure of EGFR 696-1022 L858R in complex with FIIN-3 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4r5s
TitleCrystal structure of EGFR 696-1022 L858R in complex with FIIN-3
ComponentsEpidermal growth factor receptor
KeywordsTRANSFERASE / EGFR / L858R / Kinase / FIIN-3
Function / homology
Function and homology information


positive regulation of protein kinase C activity / multivesicular body, internal vesicle lumen / negative regulation of cardiocyte differentiation / response to hydroxyisoflavone / diterpenoid metabolic process / positive regulation of prolactin secretion / Shc-EGFR complex / Inhibition of Signaling by Overexpressed EGFR / ovulation cycle / EGFR interacts with phospholipase C-gamma ...positive regulation of protein kinase C activity / multivesicular body, internal vesicle lumen / negative regulation of cardiocyte differentiation / response to hydroxyisoflavone / diterpenoid metabolic process / positive regulation of prolactin secretion / Shc-EGFR complex / Inhibition of Signaling by Overexpressed EGFR / ovulation cycle / EGFR interacts with phospholipase C-gamma / positive regulation of mucus secretion / regulation of peptidyl-tyrosine phosphorylation / epidermal growth factor binding / tongue development / response to UV-A / PLCG1 events in ERBB2 signaling / midgut development / ERBB2-EGFR signaling pathway / hydrogen peroxide metabolic process / morphogenesis of an epithelial fold / PTK6 promotes HIF1A stabilization / ERBB2 Activates PTK6 Signaling / digestive tract morphogenesis / Signaling by EGFR / response to cobalamin / intracellular vesicle / negative regulation of epidermal growth factor receptor signaling pathway / eyelid development in camera-type eye / cerebral cortex cell migration / protein insertion into membrane / ERBB2 Regulates Cell Motility / hepatocyte growth factor receptor activity / platelet-derived growth factor beta-receptor activity / placental growth factor receptor activity / brain-derived neurotrophic factor receptor activity / boss receptor activity / platelet-derived growth factor alpha-receptor activity / epidermal growth factor receptor activity / protein tyrosine kinase activator activity / Respiratory syncytial virus (RSV) attachment and entry / macrophage colony-stimulating factor receptor activity / positive regulation of bone resorption / protein tyrosine kinase collagen receptor activity / stem cell factor receptor activity / Signaling by ERBB4 / PI3K events in ERBB2 signaling / negative regulation of mitotic cell cycle / insulin-like growth factor receptor activity / transmembrane-ephrin receptor activity / positive regulation of phosphorylation / positive regulation of peptidyl-serine phosphorylation / GPI-linked ephrin receptor activity / vascular endothelial growth factor receptor activity / peptidyl-tyrosine autophosphorylation / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / hair follicle development / MAP kinase kinase kinase activity / positive regulation of G1/S transition of mitotic cell cycle / GAB1 signalosome / embryonic placenta development / fibroblast growth factor receptor activity / insulin receptor activity / salivary gland morphogenesis / positive regulation of vasoconstriction / Signaling by ERBB2 / positive regulation of glial cell proliferation / GRB2 events in EGFR signaling / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / SHC1 events in EGFR signaling / transmembrane receptor protein tyrosine kinase activity / EGFR Transactivation by Gastrin / cellular response to dexamethasone stimulus / GRB2 events in ERBB2 signaling / positive regulation of synaptic transmission, glutamatergic / SHC1 events in ERBB2 signaling / ossification / basal plasma membrane / positive regulation of DNA repair / cellular response to epidermal growth factor stimulus / positive regulation of epithelial cell proliferation / positive regulation of superoxide anion generation / positive regulation of DNA replication / epithelial cell proliferation / neuron projection morphogenesis / Signal transduction by L1 / positive regulation of smooth muscle cell proliferation / positive regulation of protein localization to plasma membrane / liver regeneration / astrocyte activation / cellular response to amino acid stimulus / NOTCH3 Activation and Transmission of Signal to the Nucleus / cellular response to estradiol stimulus / phosphatidylinositol 3-kinase/protein kinase B signal transduction / lung development / EGFR downregulation / synaptic membrane / peptidyl-tyrosine phosphorylation / clathrin-coated endocytic vesicle membrane / Signaling by ERBB2 TMD/JMD mutants / Constitutive Signaling by EGFRvIII
Similarity search - Function
: / Epidermal growth factor receptor transmembrane-juxtamembrane segment / Tyrosine protein kinase, EGF/ERB/XmrK receptor / Growth factor receptor domain 4 / Growth factor receptor domain IV / Receptor L-domain / Furin-like cysteine-rich domain / Receptor L-domain superfamily / Furin-like cysteine rich region / Receptor L domain ...: / Epidermal growth factor receptor transmembrane-juxtamembrane segment / Tyrosine protein kinase, EGF/ERB/XmrK receptor / Growth factor receptor domain 4 / Growth factor receptor domain IV / Receptor L-domain / Furin-like cysteine-rich domain / Receptor L-domain superfamily / Furin-like cysteine rich region / Receptor L domain / Furin-like repeat / Furin-like repeats / Growth factor receptor cysteine-rich domain superfamily / : / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-FI3 / Epidermal growth factor receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 3.001 Å
AuthorsZhu, S.J. / Yun, C.H.
CitationJournal: Proc.Natl.Acad.Sci.USA / Year: 2014
Title: Development of covalent inhibitors that can overcome resistance to first-generation FGFR kinase inhibitors.
Authors: Tan, L. / Wang, J. / Tanizaki, J. / Huang, Z. / Aref, A.R. / Rusan, M. / Zhu, S.J. / Zhang, Y. / Ercan, D. / Liao, R.G. / Capelletti, M. / Zhou, W. / Hur, W. / Kim, N. / Sim, T. / Gaudet, S. ...Authors: Tan, L. / Wang, J. / Tanizaki, J. / Huang, Z. / Aref, A.R. / Rusan, M. / Zhu, S.J. / Zhang, Y. / Ercan, D. / Liao, R.G. / Capelletti, M. / Zhou, W. / Hur, W. / Kim, N. / Sim, T. / Gaudet, S. / Barbie, D.A. / Yeh, J.R. / Yun, C.H. / Hammerman, P.S. / Mohammadi, M. / Janne, P.A. / Gray, N.S.
History
DepositionAug 22, 2014Deposition site: RCSB / Processing site: PDBJ
Revision 1.0Nov 12, 2014Provider: repository / Type: Initial release
Revision 1.1Aug 24, 2022Group: Database references / Derived calculations
Category: citation / database_2 ...citation / database_2 / struct_conn / struct_ref_seq_dif / struct_site
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_conn.pdbx_leaving_atom_flag / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.2Nov 20, 2024Group: Data collection / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / pdbx_entry_details / pdbx_modification_feature

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Epidermal growth factor receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,3702
Polymers37,6761
Non-polymers6941
Water39622
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)147.92, 147.92, 147.92
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number197
Space group name H-MI23

-
Components

#1: Protein Epidermal growth factor receptor / Proto-oncogene c-ErbB-1 / Receptor tyrosine-protein kinase erbB-1


Mass: 37676.484 Da / Num. of mol.: 1 / Fragment: UNP RESIDUES 696-1022 / Mutation: L858R
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: EGFR, ERBB, ERBB1, HER1 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P00533, receptor protein-tyrosine kinase
#2: Chemical ChemComp-FI3 / N-[4-({[(2,6-dichloro-3,5-dimethoxyphenyl)carbamoyl](6-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrimidin-4-yl)amino}methyl)phenyl]propanamide


Mass: 693.623 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C34H38Cl2N8O4
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 22 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 3.58 Å3/Da / Density % sol: 65.64 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 8
Details: 40% PEG 400, 150mM NaCl, 0.1M HEPES (pH 8.0), 5mM TCEP, 0.1M NDSB-211, VAPOR DIFFUSION, HANGING DROP, temperature 293K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.97913 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Mar 19, 2014
RadiationMonochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97913 Å / Relative weight: 1
ReflectionResolution: 3→50 Å / Num. obs: 267837 / % possible obs: 99.9 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3.3
Reflection shell
Resolution (Å)Diffraction-ID% possible all
3-3.23199.7
3.23-3.561100
3.56-4.07199.9
4.07-5.131100
5.13-50199.9

-
Processing

Software
NameVersionClassification
ADSCQuantumdata collection
PHENIX(phenix.refine: 1.9_1692)model building
PHENIX(phenix.refine: 1.9_1692)refinement
HKL-3000data reduction
HKL-3000data scaling
PHENIX1.9_1692phasing
RefinementMethod to determine structure: FOURIER SYNTHESIS / Resolution: 3.001→46.775 Å / SU ML: 0.49 / σ(F): 1.39 / Phase error: 26.86 / Stereochemistry target values: ML
RfactorNum. reflection% reflectionSelection details
Rfree0.239 524 4.79 %RANDOM
Rwork0.2017 ---
all0.2086 10958 --
obs0.2035 10942 99.85 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 3.001→46.775 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2367 0 48 22 2437
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0132469
X-RAY DIFFRACTIONf_angle_d1.4253348
X-RAY DIFFRACTIONf_dihedral_angle_d19.898957
X-RAY DIFFRACTIONf_chiral_restr0.069374
X-RAY DIFFRACTIONf_plane_restr0.009419
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 4 / % reflection obs: 100 %

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork
3.0006-3.30250.32671300.28972564
3.3025-3.78020.27431430.22942569
3.7802-4.7620.23041240.18292611
4.762-46.78110.2111270.18782674

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more