[English] 日本語
Yorodumi
- PDB-9fzr: Wild-type EGFR in covalent complex with Poziotinib analogue -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9fzr
TitleWild-type EGFR in covalent complex with Poziotinib analogue
ComponentsEpidermal growth factor receptor
KeywordsTRANSFERASE / EGFR / covalent / poziotinib
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 / protein tyrosine kinase activator activity / Respiratory syncytial virus (RSV) attachment and entry / positive regulation of bone resorption / Signaling by ERBB4 / PI3K events in ERBB2 signaling / negative regulation of mitotic cell cycle / positive regulation of phosphorylation / placental growth factor receptor activity / hepatocyte growth factor receptor activity / boss receptor activity / stem cell factor receptor activity / platelet-derived growth factor beta-receptor activity / brain-derived neurotrophic factor receptor activity / positive regulation of peptidyl-serine phosphorylation / platelet-derived growth factor alpha-receptor activity / epidermal growth factor receptor activity / hair follicle development / macrophage colony-stimulating factor receptor activity / peptidyl-tyrosine autophosphorylation / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / protein tyrosine kinase collagen receptor activity / MAP kinase kinase kinase activity / positive regulation of G1/S transition of mitotic cell cycle / GAB1 signalosome / transmembrane-ephrin receptor activity / insulin-like growth factor receptor activity / embryonic placenta development / vascular endothelial growth factor receptor activity / GPI-linked ephrin receptor activity / salivary gland morphogenesis / positive regulation of vasoconstriction / fibroblast growth factor receptor activity / insulin receptor activity / Signaling by ERBB2 / positive regulation of glial cell proliferation / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / transmembrane receptor protein tyrosine kinase activity / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / 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 / astrocyte activation / liver regeneration / 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 / clathrin-coated endocytic vesicle membrane / peptidyl-tyrosine phosphorylation / 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 / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
: / Epidermal growth factor receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.991 Å
AuthorsAnthony, N. / Pintar, S. / Noble, M.E.N. / Martin, M.P.
Funding support United Kingdom, 3items
OrganizationGrant numberCountry
Cancer Research UKC2115/A21421 United Kingdom
Engineering and Physical Sciences Research CouncilEP/R51309X/1 United Kingdom
Cancer Research UKDRCDDRPGMApr2020100002 United Kingdom
CitationJournal: To Be Published
Title: Insights into structure-reactivity-activity relationships for covalent inhibitors from profiling the EGFR activity of poziotinib analogues
Authors: Waring, M.
History
DepositionJul 5, 2024Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jul 16, 2025Provider: repository / Type: Initial release

-
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)37,9032
Polymers37,4581
Non-polymers4451
Water3,873215
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area16200 Å2
Unit cell
Length a, b, c (Å)145.823, 145.823, 145.823
Angle α, β, γ (deg.)90, 90, 90
Int Tables number197
Space group name H-MI23
Components on special symmetry positions
IDModelComponents
11A-1384-

HOH

-
Components

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


Mass: 37458.301 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: EGFR, ERBB, ERBB1, HER1 / Production host: Escherichia coli (E. coli)
References: UniProt: P00533, receptor protein-tyrosine kinase
#2: Chemical ChemComp-A1IHC / 1-[(3~{S})-3-[4-[(3-chloranyl-4-fluoranyl-phenyl)amino]-7-methoxy-quinazolin-6-yl]oxypyrrolidin-1-yl]propan-1-one


Mass: 444.886 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C22H22ClFN4O3 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 215 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.45 Å3/Da / Density % sol: 64.34 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 8
Details: 25mM TRIS-HCL pH8.0, 150mM NaCl, 5% Glycerol, 1mM TCEP, 100mM HEPES pH 7.4, 40% PEG400

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.898423 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Feb 12, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.898423 Å / Relative weight: 1
ReflectionResolution: 1.99→59.603 Å / Num. obs: 35412 / % possible obs: 100 % / Redundancy: 41 % / CC1/2: 1 / Rmerge(I) obs: 0.101 / Net I/σ(I): 24
Reflection shellResolution: 1.99→2.04 Å / Rmerge(I) obs: 5.43 / Num. unique obs: 105527 / CC1/2: 0.396 / % possible all: 100

-
Processing

Software
NameVersionClassification
REFMAC5.8.0430 (refmacat 0.4.82)refinement
xia2data reduction
pointlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.991→59.603 Å / Cor.coef. Fo:Fc: 0.97 / Cor.coef. Fo:Fc free: 0.952 / WRfactor Rfree: 0.211 / WRfactor Rwork: 0.168 / SU B: 4.33 / SU ML: 0.115 / Average fsc free: 0.9553 / Average fsc work: 0.9659 / Cross valid method: FREE R-VALUE / ESU R: 0.136 / ESU R Free: 0.138
Details: Hydrogens have been added in their riding positions
RfactorNum. reflection% reflection
Rfree0.2332 1773 5.007 %
Rwork0.1863 33638 -
all0.189 --
obs-35411 99.992 %
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK BULK SOLVENT
Displacement parametersBiso mean: 66.126 Å2
Baniso -1Baniso -2Baniso -3
1-0 Å20 Å20 Å2
2--0 Å20 Å2
3---0 Å2
Refinement stepCycle: LAST / Resolution: 1.991→59.603 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2593 0 31 215 2839
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0080.0122744
X-RAY DIFFRACTIONr_bond_other_d0.0010.0162641
X-RAY DIFFRACTIONr_angle_refined_deg1.7231.8373725
X-RAY DIFFRACTIONr_angle_other_deg0.5861.776102
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.1795335
X-RAY DIFFRACTIONr_dihedral_angle_2_deg12.921524
X-RAY DIFFRACTIONr_dihedral_angle_other_2_deg31.9452
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.23410498
X-RAY DIFFRACTIONr_dihedral_angle_6_deg15.30810119
X-RAY DIFFRACTIONr_chiral_restr0.0870.2407
X-RAY DIFFRACTIONr_gen_planes_refined0.0080.023203
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02595
X-RAY DIFFRACTIONr_nbd_refined0.2290.2630
X-RAY DIFFRACTIONr_symmetry_nbd_other0.1970.22594
X-RAY DIFFRACTIONr_nbtor_refined0.1850.21329
X-RAY DIFFRACTIONr_symmetry_nbtor_other0.0820.21396
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.2860.2169
X-RAY DIFFRACTIONr_symmetry_nbd_refined0.1740.236
X-RAY DIFFRACTIONr_nbd_other0.180.2126
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_refined0.2550.230
X-RAY DIFFRACTIONr_mcbond_it6.4566.4271323
X-RAY DIFFRACTIONr_mcbond_other6.4566.4281323
X-RAY DIFFRACTIONr_mcangle_it9.31811.4961663
X-RAY DIFFRACTIONr_mcangle_other9.31511.5011664
X-RAY DIFFRACTIONr_scbond_it6.7716.8071421
X-RAY DIFFRACTIONr_scbond_other6.7696.8081422
X-RAY DIFFRACTIONr_scangle_it10.05212.2482062
X-RAY DIFFRACTIONr_scangle_other10.04912.2472063
X-RAY DIFFRACTIONr_lrange_it14.26668.5333222
X-RAY DIFFRACTIONr_lrange_other14.26568.5343223
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 20

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRfactor allNum. reflection allFsc freeFsc work% reflection obs (%)WRfactor Rwork
1.991-2.0420.3421330.33924910.33926250.9150.91499.96190.342
2.042-2.0980.3291340.31323820.31425160.9280.9321000.315
2.098-2.1590.2691350.2823440.27924790.9470.9471000.274
2.159-2.2250.2941210.25522580.25723790.940.9561000.24
2.225-2.2980.281010.2322210.23223220.950.9651000.21
2.298-2.3790.247920.22121600.22222520.9610.9691000.198
2.379-2.4680.2221030.2120650.21121680.9670.9741000.185
2.468-2.5690.2931060.1919710.19520770.9560.9781000.165
2.569-2.6830.2321020.18719100.1920120.9660.9781000.163
2.683-2.8140.267870.18218330.18519200.9560.9791000.16
2.814-2.9650.2311000.18517000.18718000.9660.9791000.164
2.965-3.1450.216940.18916490.19117430.9710.9781000.171
3.145-3.3610.226790.19215380.19416170.9690.9781000.179
3.361-3.630.256960.19114270.19515230.9660.9791000.178
3.63-3.9750.248810.18913340.19314150.9620.981000.181
3.975-4.4410.226510.15812040.16112550.9710.9861000.151
4.441-5.1240.181650.1410740.14211390.980.9881000.135
5.124-6.2640.252440.1859240.1889680.980.9831000.177
6.264-8.810.218350.1667190.1697540.9630.9851000.16
8.81-59.6030.117140.1714360.1694500.9930.9821000.167

+
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