[English] 日本語
Yorodumi
- PDB-5gty: Crystal structure of EGFR 696-1022 T790M in complex with LXX-6-26 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5gty
TitleCrystal structure of EGFR 696-1022 T790M in complex with LXX-6-26
ComponentsEpidermal growth factor receptor
KeywordsTRANSFERASE / EGFR / T790M / LXX-6-26 / inhibitor
Function / homology
Function and homology information


positive regulation of protein kinase C activity / multivesicular body, internal vesicle lumen / positive regulation of prolactin secretion / negative regulation of cardiocyte differentiation / response to hydroxyisoflavone / diterpenoid metabolic process / 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 / positive regulation of prolactin secretion / negative regulation of cardiocyte differentiation / response to hydroxyisoflavone / diterpenoid metabolic process / Shc-EGFR complex / Inhibition of Signaling by Overexpressed EGFR / ovulation cycle / EGFR interacts with phospholipase C-gamma / positive regulation of mucus secretion / epidermal growth factor binding / regulation of peptidyl-tyrosine phosphorylation / 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 / eyelid development in camera-type eye / negative regulation of epidermal growth factor receptor signaling pathway / cerebral cortex cell migration / protein insertion into membrane / ERBB2 Regulates Cell Motility / protein tyrosine kinase activator activity / Respiratory syncytial virus (RSV) attachment and entry / Signaling by ERBB4 / PI3K events in ERBB2 signaling / negative regulation of mitotic cell cycle / MAP kinase kinase kinase activity / hair follicle development / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / positive regulation of G1/S transition of mitotic cell cycle / positive regulation of bone resorption / GAB1 signalosome / embryonic placenta development / positive regulation of phosphorylation / salivary gland morphogenesis / peptidyl-tyrosine autophosphorylation / positive regulation of peptidyl-serine phosphorylation / positive regulation of glial cell proliferation / positive regulation of vasoconstriction / Signaling by ERBB2 / transmembrane receptor protein tyrosine kinase activity / GRB2 events in EGFR signaling / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / SHC1 events in EGFR signaling / EGFR Transactivation by Gastrin / GRB2 events in ERBB2 signaling / cellular response to epidermal growth factor stimulus / SHC1 events in ERBB2 signaling / cellular response to dexamethasone stimulus / ossification / positive regulation of DNA repair / positive regulation of synaptic transmission, glutamatergic / neuron projection morphogenesis / positive regulation of superoxide anion generation / positive regulation of epithelial cell proliferation / epithelial cell proliferation / liver regeneration / basal plasma membrane / Signal transduction by L1 / positive regulation of DNA replication / positive regulation of protein localization to plasma membrane / astrocyte activation / NOTCH3 Activation and Transmission of Signal to the Nucleus / phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of smooth muscle cell proliferation / cellular response to amino acid stimulus / cellular response to estradiol stimulus / lung development / EGFR downregulation / placental growth factor receptor activity / clathrin-coated endocytic vesicle membrane / Signaling by ERBB2 TMD/JMD mutants / synaptic membrane / vascular endothelial growth factor receptor activity / hepatocyte growth factor receptor activity / macrophage colony-stimulating factor receptor activity / platelet-derived growth factor alpha-receptor activity / platelet-derived growth factor beta-receptor activity / boss receptor activity / protein tyrosine kinase collagen receptor activity / brain-derived neurotrophic factor receptor activity / stem cell factor receptor activity / GPI-linked ephrin receptor activity / transmembrane-ephrin receptor activity / epidermal growth factor receptor activity / fibroblast growth factor receptor activity / insulin receptor activity / insulin-like growth factor receptor activity / Constitutive Signaling by EGFRvIII / Signaling by ERBB2 ECD mutants
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-816 / Epidermal growth factor receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.14 Å
AuthorsYan, X.E. / Yun, C.H.
CitationJournal: Oncotarget / Year: 2017
Title: Discovery and characterization of a novel irreversible EGFR mutants selective and potent kinase inhibitor CHMFL-EGFR-26 with a distinct binding mode.
Authors: Hu, C. / Wang, A. / Wu, H. / Qi, Z. / Li, X. / Yan, X.E. / Chen, C. / Yu, K. / Zou, F. / Wang, W. / Wang, W. / Wu, J. / Liu, J. / Wang, B. / Wang, L. / Ren, T. / Zhang, S. / Yun, C.H. / Liu, J. / Liu, Q.
History
DepositionAug 23, 2016Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Sep 6, 2017Provider: repository / Type: Initial release
Revision 1.1Oct 4, 2017Group: Data collection / Category: diffrn_detector / Item: _diffrn_detector.detector
Revision 1.2Nov 29, 2017Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.3Nov 8, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.4Oct 9, 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
D: Epidermal growth factor receptor
E: Epidermal growth factor receptor
F: Epidermal growth factor receptor
G: Epidermal growth factor receptor
H: Epidermal growth factor receptor
C: Epidermal growth factor receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)305,48520
Polymers301,2058
Non-polymers4,28012
Water5,459303
1
A: Epidermal growth factor receptor
E: Epidermal growth factor receptor
H: Epidermal growth factor receptor
C: Epidermal growth factor receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)152,80511
Polymers150,6024
Non-polymers2,2027
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Epidermal growth factor receptor
D: Epidermal growth factor receptor
F: Epidermal growth factor receptor
G: Epidermal growth factor receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)152,6809
Polymers150,6024
Non-polymers2,0785
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)117.427, 71.796, 152.530
Angle α, β, γ (deg.)90.00, 103.53, 90.00
Int Tables number4
Space group name H-MP1211

-
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.: 8 / Fragment: UNP RESIDUES 696-1022
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-816 / 1-[(3R)-3-[4-azanyl-3-[3-chloranyl-4-[(6-methylpyridin-2-yl)methoxy]phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one


Mass: 503.983 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: C26H26ClN7O2
#3: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C2H6O2
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 303 / 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: 2.08 Å3/Da / Density % sol: 40.74 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 6.2
Details: 0.05M CaCl2, 0.1M B-Tris pH 6.2, 24% PEG 550MME, 5mM TCEP

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL19U1 / Wavelength: 0.97776 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Jan 10, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97776 Å / Relative weight: 1
ReflectionResolution: 3.15→50 Å / Num. obs: 42443 / % possible obs: 98.2 % / Redundancy: 5.1 % / Net I/σ(I): 6.14
Reflection shellResolution: 3.15→3.26 Å

-
Processing

Software
NameVersionClassification
PHENIX(dev_2400)refinement
DENZOdata reduction
HKL-3000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2JIT

2jit


Resolution: 3.14→49.81 Å / SU ML: 0.38 / Cross valid method: FREE R-VALUE / σ(F): 1.97 / Phase error: 34.54 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2795 2094 5.04 %
Rwork0.2566 --
obs0.2578 41554 95.18 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 3.14→49.81 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms18649 0 304 303 19256
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0119400
X-RAY DIFFRACTIONf_angle_d1.34226317
X-RAY DIFFRACTIONf_dihedral_angle_d28.2147344
X-RAY DIFFRACTIONf_chiral_restr0.0872955
X-RAY DIFFRACTIONf_plane_restr0.0133290
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
3.1402-3.21330.34681410.29252121X-RAY DIFFRACTION79
3.2133-3.29360.33791240.30482548X-RAY DIFFRACTION92
3.2936-3.38270.32591320.2772577X-RAY DIFFRACTION94
3.3827-3.48220.30391240.26882591X-RAY DIFFRACTION94
3.4822-3.59450.32621350.26082596X-RAY DIFFRACTION94
3.5945-3.7230.32071380.26042596X-RAY DIFFRACTION95
3.723-3.8720.29251430.24972643X-RAY DIFFRACTION97
3.872-4.04810.24671270.22832718X-RAY DIFFRACTION97
4.0481-4.26140.22531490.21532679X-RAY DIFFRACTION98
4.2614-4.52830.231340.21752748X-RAY DIFFRACTION99
4.5283-4.87760.26731550.23442704X-RAY DIFFRACTION98
4.8776-5.3680.25891720.24332690X-RAY DIFFRACTION99
5.368-6.14350.26361260.2692789X-RAY DIFFRACTION99
6.1435-7.73550.28611460.29592777X-RAY DIFFRACTION99
7.7355-49.81670.2961480.28942683X-RAY DIFFRACTION93

+
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