[English] 日本語
Yorodumi
- PDB-5j9z: EGFR-T790M in complex with pyrazolopyrimidine inhibitor 1a -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5j9z
TitleEGFR-T790M in complex with pyrazolopyrimidine inhibitor 1a
ComponentsEpidermal growth factor receptor
KeywordsTRANSFERASE / tyrosine kinase / covalent inhibitor / drug resistance
Function / homology
Function and homology information


response to hydroxyisoflavone / negative regulation of cardiocyte differentiation / activation of phospholipase A2 activity by calcium-mediated signaling / multivesicular body, internal vesicle lumen / positive regulation of prolactin secretion / epidermal growth factor-activated receptor activity / Shc-EGFR complex / diterpenoid metabolic process / ovulation cycle / positive regulation of protein kinase C activity ...response to hydroxyisoflavone / negative regulation of cardiocyte differentiation / activation of phospholipase A2 activity by calcium-mediated signaling / multivesicular body, internal vesicle lumen / positive regulation of prolactin secretion / epidermal growth factor-activated receptor activity / Shc-EGFR complex / diterpenoid metabolic process / ovulation cycle / positive regulation of protein kinase C activity / Inhibition of Signaling by Overexpressed EGFR / positive regulation of mucus secretion / EGFR interacts with phospholipase C-gamma / magnesium ion homeostasis / epidermal growth factor binding / regulation of phosphatidylinositol 3-kinase signaling / response to UV-A / tongue development / PLCG1 events in ERBB2 signaling / PTK6 promotes HIF1A stabilization / intracellular vesicle / midgut development / hydrogen peroxide metabolic process / regulation of nitric-oxide synthase activity / ERBB2 Activates PTK6 Signaling / Signaling by EGFR / Signaling by ERBB4 / response to cobalamin / negative regulation of epidermal growth factor receptor signaling pathway / ERBB2 Regulates Cell Motility / protein insertion into membrane / MAP kinase kinase kinase activity / regulation of JNK cascade / PI3K events in ERBB2 signaling / activation of phospholipase C activity / positive regulation of glial cell proliferation / response to osmotic stress / hair follicle development / negative regulation of mitotic cell cycle / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / GAB1 signalosome / positive regulation of G1/S transition of mitotic cell cycle / positive regulation of synaptic transmission, glutamatergic / positive regulation of vasoconstriction / positive regulation of nitric oxide mediated signal transduction / positive regulation of production of miRNAs involved in gene silencing by miRNA / regulation of peptidyl-tyrosine phosphorylation / positive regulation of DNA repair / positive regulation of cyclin-dependent protein serine/threonine kinase activity / peptidyl-tyrosine autophosphorylation / cellular response to dexamethasone stimulus / positive regulation of DNA replication / GRB2 events in EGFR signaling / basal plasma membrane / SHC1 events in EGFR signaling / Signaling by ERBB2 / EGFR Transactivation by Gastrin / GRB2 events in ERBB2 signaling / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / ossification / astrocyte activation / SHC1 events in ERBB2 signaling / regulation of ERK1 and ERK2 cascade / cellular response to epidermal growth factor stimulus / neuron projection morphogenesis / cellular response to estradiol stimulus / NOTCH3 Activation and Transmission of Signal to the Nucleus / positive regulation of phosphorylation / positive regulation of epithelial cell proliferation / Signal transduction by L1 / positive regulation of superoxide anion generation / cellular response to cadmium ion / clathrin-coated endocytic vesicle membrane / liver regeneration / cell-cell adhesion / EGFR downregulation / positive regulation of protein localization to plasma membrane / cellular response to reactive oxygen species / Signaling by ERBB2 TMD/JMD mutants / HCMV Early Events / Constitutive Signaling by EGFRvIII / Signaling by ERBB2 ECD mutants / Signaling by ERBB2 KD Mutants / lung development / ruffle membrane / positive regulation of smooth muscle cell proliferation / positive regulation of NIK/NF-kappaB signaling / receptor protein-tyrosine kinase / response to calcium ion / negative regulation of protein catabolic process / Downregulation of ERBB2 signaling / epidermal growth factor receptor signaling pathway / positive regulation of bone resorption / positive regulation of inflammatory response / circadian rhythm / positive regulation of canonical Wnt signaling pathway / vasodilation / positive regulation of kinase activity / kinase binding / cellular response to xenobiotic stimulus => GO:0071466
Similarity search - Function
Tyrosine protein kinase, EGF/ERB/XmrK receptor / Growth factor receptor domain 4 / Growth factor receptor domain IV / Receptor L domain / Receptor L-domain / Furin-like cysteine-rich domain / Receptor L-domain superfamily / Furin-like cysteine rich region / Furin-like repeats / Furin-like repeat ...Tyrosine protein kinase, EGF/ERB/XmrK receptor / Growth factor receptor domain 4 / Growth factor receptor domain IV / Receptor L domain / Receptor L-domain / Furin-like cysteine-rich domain / Receptor L-domain superfamily / Furin-like cysteine rich region / Furin-like repeats / Furin-like repeat / 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 / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Protein kinases ATP-binding region signature. / Protein kinase, ATP binding site / 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-6HJ / Epidermal growth factor receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.5 Å
AuthorsBecker, C. / Engel, J. / Rauh, D.
CitationJournal: Angew.Chem.Int.Ed.Engl. / Year: 2016
Title: Insight into the Inhibition of Drug-Resistant Mutants of the Receptor Tyrosine Kinase EGFR.
Authors: Engel, J. / Becker, C. / Lategahn, J. / Keul, M. / Ketzer, J. / Muhlenberg, T. / Kollipara, L. / Schultz-Fademrecht, C. / Zahedi, R.P. / Bauer, S. / Rauh, D.
History
DepositionApr 11, 2016Deposition site: RCSB / Processing site: PDBE
Revision 1.0Aug 17, 2016Provider: repository / Type: Initial release
Revision 1.1Sep 7, 2016Group: Database references
Revision 1.2Feb 20, 2019Group: Advisory / Data collection / Derived calculations
Category: database_PDB_remark / pdbx_data_processing_status ...database_PDB_remark / pdbx_data_processing_status / pdbx_validate_symm_contact / struct_conn
Item: _database_PDB_remark.text

-
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)37,5512
Polymers37,1491
Non-polymers4011
Water37821
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area14890 Å2
MethodPISA
Unit cell
γ
α
β
Length a, b, c (Å)146.460, 146.460, 146.460
Angle α, β, γ (deg.)90.000, 90.000, 90.000
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: 37149.039 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: Spodoptera frugiperda (fall armyworm)
References: UniProt: P00533, receptor protein-tyrosine kinase
#2: Chemical ChemComp-6HJ / (R)-1-(3-(4-amino-3-(1-methyl-1H-indol-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one


Mass: 401.464 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C22H23N7O
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 21 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.39 Å3/Da / Density % sol: 63.75 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / Details: 100 mM MES, 900 mM - 1100 mM Na/K-tartrate / PH range: 7.0-7.3

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 0.91884 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Apr 16, 2014
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.91884 Å / Relative weight: 1
ReflectionResolution: 2.5→46.31 Å / Num. obs: 18225 / % possible obs: 100 % / Observed criterion σ(I): -3 / Redundancy: 40.65 % / Biso Wilson estimate: 58.003 Å2 / CC1/2: 1 / Rmerge(I) obs: 0.137 / Net I/σ(I): 28.39
Reflection shell
Resolution (Å)Highest resolution (Å)Rmerge(I) obsMean I/σ(I) obsDiffraction-ID% possible all
2.5-2.571.6472.761100
2.57-2.641.2493.781100
2.64-2.711.0434.591100
2.71-2.80.8585.61100
2.8-2.890.6647.461100
2.89-2.990.48610.491100
2.99-3.10.40812.71100
3.1-3.230.30217.15198.9
3.23-3.370.22722.681100
3.37-3.540.17128.91100
3.54-3.730.12836.591100
3.73-3.950.10344.871100
3.95-4.230.08454.241100
4.23-4.570.07460.121100
4.57-50.06566.691100
5-5.590.06860.661100
5.59-6.460.0760.71100
6.46-7.910.05774.511100
7.91-11.180.03999.891100
11.180.039101.65198.3

-
Processing

Software
NameVersionClassification
REFMAC5.8.0135refinement
XSCALENov. 2013data scaling
PDB_EXTRACT3.2data extraction
XDSNov. 2013data reduction
PHASER2.5.1phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3vjo

3vjo


Resolution: 2.5→46.31 Å / Cor.coef. Fo:Fc: 0.955 / Cor.coef. Fo:Fc free: 0.936 / SU B: 8.91 / SU ML: 0.19 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.276 / ESU R Free: 0.226
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2391 912 5 %RANDOM
Rwork0.1961 ---
obs0.1982 17313 99.98 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso max: 200.63 Å2 / Biso mean: 60.698 Å2 / Biso min: 31.75 Å2
Baniso -1Baniso -2Baniso -3
1-0 Å20 Å20 Å2
2--0 Å20 Å2
3---0 Å2
Refinement stepCycle: final / Resolution: 2.5→46.31 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2333 0 30 21 2384
Biso mean--53.26 50.74 -
Num. residues----291
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0170.0192417
X-RAY DIFFRACTIONr_bond_other_d0.0090.022377
X-RAY DIFFRACTIONr_angle_refined_deg1.7751.9943272
X-RAY DIFFRACTIONr_angle_other_deg2.7533.0045479
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.4865288
X-RAY DIFFRACTIONr_dihedral_angle_2_deg36.09724.059101
X-RAY DIFFRACTIONr_dihedral_angle_3_deg12.92215444
X-RAY DIFFRACTIONr_dihedral_angle_4_deg13.2681515
X-RAY DIFFRACTIONr_chiral_restr0.0930.2364
X-RAY DIFFRACTIONr_gen_planes_refined0.010.0212631
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02515
X-RAY DIFFRACTIONr_mcbond_it5.5065.7571161
X-RAY DIFFRACTIONr_mcbond_other5.4995.7541160
X-RAY DIFFRACTIONr_mcangle_it8.4968.6021446
LS refinement shellResolution: 2.501→2.566 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.384 66 -
Rwork0.336 1250 -
all-1316 -
obs--100 %

+
About Yorodumi

-
News

-
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

+
Jun 16, 2017. Omokage search with filter

Omokage search with filter

Result of Omokage search can be filtered by keywords and the database types

Related info.:Omokage search

-
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