[English] 日本語
Yorodumi
- PDB-5yu9: Crystal structure of EGFR 696-1022 T790M in complex with Ibrutinib -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5yu9
TitleCrystal structure of EGFR 696-1022 T790M in complex with Ibrutinib
ComponentsEpidermal growth factor receptor
KeywordsONCOPROTEIN / EGFR / T790M / ibrutinib / inhibitor
Function / homology
Function and homology information


multivesicular body, internal vesicle lumen / negative regulation of cardiocyte differentiation / Developmental Lineage of Mammary Gland Myoepithelial Cells / Shc-EGFR complex / positive regulation of protein kinase C signaling / Inhibition of Signaling by Overexpressed EGFR / epidermal growth factor receptor activity / EGFR interacts with phospholipase C-gamma / regulation of peptidyl-tyrosine phosphorylation / epidermal growth factor binding ...multivesicular body, internal vesicle lumen / negative regulation of cardiocyte differentiation / Developmental Lineage of Mammary Gland Myoepithelial Cells / Shc-EGFR complex / positive regulation of protein kinase C signaling / Inhibition of Signaling by Overexpressed EGFR / epidermal growth factor receptor activity / EGFR interacts with phospholipase C-gamma / regulation of peptidyl-tyrosine phosphorylation / epidermal growth factor binding / response to UV-A / ubiquitin-dependent endocytosis / PLCG1 events in ERBB2 signaling / ERBB2-EGFR signaling pathway / morphogenesis of an epithelial fold / PTK6 promotes HIF1A stabilization / Signaling by EGFR / ERBB2 Activates PTK6 Signaling / digestive tract morphogenesis / intracellular vesicle / eyelid development in camera-type eye / cerebral cortex cell migration / ERBB2 Regulates Cell Motility / protein insertion into membrane / negative regulation of epidermal growth factor receptor signaling pathway / protein tyrosine kinase activator activity / Respiratory syncytial virus (RSV) attachment and entry / Signaling by ERBB4 / PI3K events in ERBB2 signaling / positive regulation of phosphorylation / positive regulation of peptidyl-serine phosphorylation / hair follicle development / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / MAP kinase kinase kinase activity / positive regulation of G1/S transition of mitotic cell cycle / GAB1 signalosome / embryonic placenta development / xenobiotic transport / salivary gland morphogenesis / positive regulation of epidermal growth factor receptor signaling pathway / sperm end piece / Signaling by ERBB2 / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / transmembrane receptor protein tyrosine kinase activity / EGFR Transactivation by Gastrin / GRB2 events in ERBB2 signaling / SHC1 events in ERBB2 signaling / sperm principal piece / ossification / basal plasma membrane / cellular response to epidermal growth factor stimulus / epithelial cell proliferation / positive regulation of DNA replication / positive regulation of DNA repair / positive regulation of epithelial cell proliferation / Signal transduction by L1 / positive regulation of protein localization to plasma membrane / phosphatidylinositol 3-kinase/protein kinase B signal transduction / NOTCH3 Activation and Transmission of Signal to the Nucleus / cellular response to estradiol stimulus / cellular response to amino acid stimulus / clathrin-coated endocytic vesicle membrane / EGFR downregulation / Signaling by ERBB2 TMD/JMD mutants / cell-cell adhesion / Constitutive Signaling by EGFRvIII / receptor protein-tyrosine kinase / Signaling by ERBB2 ECD mutants / Signaling by ERBB2 KD Mutants / negative regulation of protein catabolic process / positive regulation of miRNA transcription / epidermal growth factor receptor signaling pathway / kinase binding / Downregulation of ERBB2 signaling / ruffle membrane / positive regulation of fibroblast proliferation / cell morphogenesis / positive regulation of protein phosphorylation / Constitutive Signaling by Aberrant PI3K in Cancer / neuron differentiation / HCMV Early Events / actin filament binding / transmembrane signaling receptor activity / cell junction / positive regulation of canonical Wnt signaling pathway / sperm midpiece / PIP3 activates AKT signaling / Cargo recognition for clathrin-mediated endocytosis / Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants / Clathrin-mediated endocytosis / ATPase binding / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / virus receptor activity / positive regulation of cell growth / RAF/MAP kinase cascade / protein tyrosine kinase activity / double-stranded DNA binding / early endosome membrane
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-1E8 / Epidermal growth factor receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.95 Å
AuthorsYan, X.E. / Yun, C.H.
CitationJournal: Oncotarget / Year: 2016
Title: Ibrutinib targets mutant-EGFR kinase with a distinct binding conformation.
Authors: Wang, A. / Yan, X.E. / Wu, H. / Wang, W. / Hu, C. / Chen, C. / Zhao, Z. / Zhao, P. / Li, X. / Wang, L. / Wang, B. / Ye, Z. / Wang, J. / Wang, C. / Zhang, W. / Gray, N.S. / Weisberg, E.L. / ...Authors: Wang, A. / Yan, X.E. / Wu, H. / Wang, W. / Hu, C. / Chen, C. / Zhao, Z. / Zhao, P. / Li, X. / Wang, L. / Wang, B. / Ye, Z. / Wang, J. / Wang, C. / Zhang, W. / Gray, N.S. / Weisberg, E.L. / Chen, L. / Liu, J. / Yun, C.H. / Liu, Q.
History
DepositionNov 21, 2017Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Dec 27, 2017Provider: repository / Type: Initial release
Revision 1.1Nov 22, 2023Group: Data collection / Database references ...Data collection / Database references / Refinement description / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _chem_comp.pdbx_synonyms / _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.2Nov 6, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Epidermal growth factor receptor
B: Epidermal growth factor receptor
C: Epidermal growth factor receptor
D: Epidermal growth factor receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)152,47111
Polymers150,6024
Non-polymers1,8687
Water17,114950
1
A: Epidermal growth factor receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,0912
Polymers37,6511
Non-polymers4401
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Epidermal growth factor receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,0912
Polymers37,6511
Non-polymers4401
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
C: Epidermal growth factor receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,1624
Polymers37,6511
Non-polymers5113
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
4
D: Epidermal growth factor receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,1273
Polymers37,6511
Non-polymers4762
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)168.194, 74.385, 120.460
Angle α, β, γ (deg.)90.00, 118.32, 90.00
Int Tables number5
Space group name H-MC121
Components on special symmetry positions
IDModelComponents
11C-1103-

CL

-
Components

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


Mass: 37650.598 Da / Num. of mol.: 4 / Mutation: T790M
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-1E8 / 1-{(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl}prop-2-en-1-one / Imbruvica / PCI-32765


Mass: 440.497 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C25H24N6O2
#3: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: Cl
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 950 / 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: 2.2 Å3/Da / Density % sol: 44.04 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 5
Details: 0.1 M sodium citrate (pH 5.0), 12% PEG 10000, 3% dioxane, 5 mM TCEP

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL17U1 / Wavelength: 0.9793 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Jan 26, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9793 Å / Relative weight: 1
ReflectionResolution: 1.95→50 Å / Num. obs: 94954 / % possible obs: 99.42 % / Redundancy: 3.2 % / Rpim(I) all: 0.095 / Net I/σ(I): 7.9
Reflection shellResolution: 1.95→2.02 Å

-
Processing

Software
NameVersionClassification
PHENIX(dev_2400)refinement
DENZOdata reduction
HKL-2000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3IKA

3ika


Resolution: 1.95→41.628 Å / SU ML: 0.21 / Cross valid method: FREE R-VALUE / σ(F): 1.98 / Phase error: 22.95 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2215 4744 5 %
Rwork0.2019 --
obs0.2029 94954 99.42 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 1.95→41.628 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms9611 0 135 950 10696
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.01210063
X-RAY DIFFRACTIONf_angle_d1.38713643
X-RAY DIFFRACTIONf_dihedral_angle_d26.0593956
X-RAY DIFFRACTIONf_chiral_restr0.1121528
X-RAY DIFFRACTIONf_plane_restr0.0091705
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.95-1.97220.27971400.26432894X-RAY DIFFRACTION97
1.9722-1.99540.31570.26423041X-RAY DIFFRACTION100
1.9954-2.01970.28561500.26122990X-RAY DIFFRACTION100
2.0197-2.04530.2991780.25052988X-RAY DIFFRACTION100
2.0453-2.07220.22851540.2452990X-RAY DIFFRACTION100
2.0722-2.10060.28091630.23893006X-RAY DIFFRACTION100
2.1006-2.13060.24931410.22353025X-RAY DIFFRACTION100
2.1306-2.16240.24811440.22842989X-RAY DIFFRACTION100
2.1624-2.19620.25031490.21483046X-RAY DIFFRACTION100
2.1962-2.23220.21511610.20482978X-RAY DIFFRACTION99
2.2322-2.27070.22951500.21273017X-RAY DIFFRACTION100
2.2707-2.3120.241780.21272982X-RAY DIFFRACTION100
2.312-2.35640.27261660.21723016X-RAY DIFFRACTION100
2.3564-2.40450.24141600.22023005X-RAY DIFFRACTION100
2.4045-2.45680.23731460.21652993X-RAY DIFFRACTION100
2.4568-2.51390.25471670.21553005X-RAY DIFFRACTION100
2.5139-2.57680.21851670.22072995X-RAY DIFFRACTION100
2.5768-2.64650.23231620.20823007X-RAY DIFFRACTION100
2.6465-2.72430.22191510.20382987X-RAY DIFFRACTION100
2.7243-2.81220.24461550.21263045X-RAY DIFFRACTION100
2.8122-2.91270.24351900.20592971X-RAY DIFFRACTION100
2.9127-3.02930.24091580.20263012X-RAY DIFFRACTION100
3.0293-3.16710.21111380.19583053X-RAY DIFFRACTION100
3.1671-3.3340.19991680.193007X-RAY DIFFRACTION100
3.334-3.54280.19411650.18833045X-RAY DIFFRACTION100
3.5428-3.81620.22541770.17623000X-RAY DIFFRACTION99
3.8162-4.19990.15671550.16063004X-RAY DIFFRACTION99
4.1999-4.80690.171630.16653039X-RAY DIFFRACTION99
4.8069-6.05320.20651530.19213043X-RAY DIFFRACTION99
6.0532-41.63790.23771380.21823037X-RAY DIFFRACTION96

+
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