[English] 日本語
Yorodumi
- PDB-5hcx: EGFR kinase domain mutant "TMLR" with azabenzimidazole compound 7 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5hcx
TitleEGFR kinase domain mutant "TMLR" with azabenzimidazole compound 7
ComponentsEpidermal growth factor receptor
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / protein kinase / inhibitor / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


response to hydroxyisoflavone / multivesicular body, internal vesicle lumen / positive regulation of protein kinase C activity / positive regulation of prolactin secretion / negative regulation of cardiocyte differentiation / diterpenoid metabolic process / Shc-EGFR complex / ovulation cycle / Inhibition of Signaling by Overexpressed EGFR / epidermal growth factor receptor activity ...response to hydroxyisoflavone / multivesicular body, internal vesicle lumen / positive regulation of protein kinase C activity / positive regulation of prolactin secretion / negative regulation of cardiocyte differentiation / diterpenoid metabolic process / Shc-EGFR complex / ovulation cycle / Inhibition of Signaling by Overexpressed EGFR / epidermal growth factor receptor activity / EGFR interacts with phospholipase C-gamma / positive regulation of mucus secretion / epidermal growth factor binding / response to UV-A / tongue development / PLCG1 events in ERBB2 signaling / midgut development / hydrogen peroxide metabolic process / ERBB2-EGFR signaling pathway / regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / PTK6 promotes HIF1A stabilization / digestive tract morphogenesis / morphogenesis of an epithelial fold / ERBB2 Activates PTK6 Signaling / intracellular vesicle / Signaling by EGFR / protein tyrosine kinase activator activity / transmembrane receptor protein tyrosine kinase activator activity / negative regulation of epidermal growth factor receptor signaling pathway / response to cobalamin / Signaling by ERBB4 / eyelid development in camera-type eye / protein insertion into membrane / cerebral cortex cell migration / ERBB2 Regulates Cell Motility / Respiratory syncytial virus (RSV) attachment and entry / regulation of JNK cascade / PI3K events in ERBB2 signaling / positive regulation of cyclin-dependent protein serine/threonine kinase activity / negative regulation of mitotic cell cycle / MAP kinase kinase kinase activity / hair follicle development / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / embryonic placenta development / positive regulation of bone resorption / GAB1 signalosome / positive regulation of G1/S transition of mitotic cell cycle / salivary gland morphogenesis / peptidyl-tyrosine autophosphorylation / positive regulation of phosphorylation / regulation of peptidyl-tyrosine phosphorylation / positive regulation of glial cell proliferation / positive regulation of vasoconstriction / Signaling by ERBB2 / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / EGFR Transactivation by Gastrin / cellular response to epidermal growth factor stimulus / cellular response to cadmium ion / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / GRB2 events in ERBB2 signaling / transmembrane receptor protein tyrosine kinase activity / positive regulation of DNA repair / regulation of ERK1 and ERK2 cascade / SHC1 events in ERBB2 signaling / ossification / cellular response to dexamethasone stimulus / neurogenesis / positive regulation of synaptic transmission, glutamatergic / positive regulation of epithelial cell proliferation / neuron projection morphogenesis / basal plasma membrane / epithelial cell proliferation / positive regulation of superoxide anion generation / positive regulation of DNA replication / Signal transduction by L1 / cellular response to estradiol stimulus / NOTCH3 Activation and Transmission of Signal to the Nucleus / astrocyte activation / liver regeneration / cellular response to amino acid stimulus / positive regulation of protein localization to plasma membrane / Signaling by ERBB2 TMD/JMD mutants / lung development / EGFR downregulation / positive regulation of smooth muscle cell proliferation / positive regulation of MAP kinase activity / Constitutive Signaling by EGFRvIII / clathrin-coated endocytic vesicle membrane / Signaling by ERBB2 ECD mutants / epidermal growth factor receptor signaling pathway / Signaling by ERBB2 KD Mutants / receptor protein-tyrosine kinase / negative regulation of protein catabolic process / kinase binding / Downregulation of ERBB2 signaling / positive regulation of miRNA transcription / peptidyl-tyrosine phosphorylation / cell-cell adhesion / ruffle 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 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; 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-60B / Epidermal growth factor receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.6 Å
AuthorsEigenbrot, C. / Yu, C.
CitationJournal: J.Med.Chem. / Year: 2016
Title: Discovery of a Noncovalent, Mutant-Selective Epidermal Growth Factor Receptor Inhibitor.
Authors: Chan, B.K. / Hanan, E.J. / Bowman, K.K. / Bryan, M.C. / Burdick, D. / Chan, E. / Chen, Y. / Clausen, S. / Dela Vega, T. / Dotson, J. / Eigenbrot, C. / Elliott, R.L. / Heald, R.A. / Jackson, ...Authors: Chan, B.K. / Hanan, E.J. / Bowman, K.K. / Bryan, M.C. / Burdick, D. / Chan, E. / Chen, Y. / Clausen, S. / Dela Vega, T. / Dotson, J. / Eigenbrot, C. / Elliott, R.L. / Heald, R.A. / Jackson, P.S. / Knight, J.D. / La, H. / Lainchbury, M.D. / Malek, S. / Purkey, H.E. / Schaefer, G. / Schmidt, S. / Seward, E.M. / Sideris, S. / Shao, L. / Wang, S. / Yeap, S.K. / Yen, I. / Yu, C. / Heffron, T.P.
History
DepositionJan 4, 2016Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 7, 2016Provider: repository / Type: Initial release
Revision 1.1Oct 26, 2016Group: Database references
Revision 1.2Sep 27, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / citation / database_2 / pdbx_initial_refinement_model / pdbx_struct_oper_list
Item: _citation.journal_id_CSD / _database_2.pdbx_DOI ..._citation.journal_id_CSD / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_oper_list.symmetry_operation

-
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)38,0843
Polymers37,5491
Non-polymers5352
Water1267
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area190 Å2
ΔGint-14 kcal/mol
Surface area15310 Å2
MethodPISA
Unit cell
Length a, b, c (Å)146.744, 146.744, 146.744
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: 37549.398 Da / Num. of mol.: 1 / Mutation: T790M,L858R,A865E, A866E, A867K
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-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#3: Chemical ChemComp-60B / ~{N}-[2-(1-cyclopropylsulfonylpyrazol-4-yl)pyrimidin-4-yl]-2-methyl-1-propan-2-yl-imidazo[4,5-c]pyridin-6-amine


Mass: 438.506 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H22N8O2S
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 7 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION

-
Sample preparation

CrystalDensity Matthews: 3.51 Å3/Da / Density % sol: 64.92 %
Crystal growTemperature: 292 K / Method: vapor diffusion, hanging drop / pH: 7.5 / Details: PEG 10K, ethylene glycol

-
Data collection

DiffractionMean temperature: 110 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 0.9774 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Dec 11, 2013
RadiationMonochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9774 Å / Relative weight: 1
ReflectionResolution: 2.6→24.08 Å / Num. all: 15892 / Num. obs: 15892 / % possible obs: 98 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 6.2 % / Biso Wilson estimate: 77.22 Å2 / Rsym value: 0.094 / Net I/σ(I): 16.7
Reflection shellResolution: 2.6→2.7 Å / Redundancy: 6.2 % / Rmerge(I) obs: 0.816 / Mean I/σ(I) obs: 2.2 / % possible all: 99.5

-
Processing

Software
NameVersionClassification
BUSTER2.11.4refinement
HKL-2000data reduction
SCALEPACKdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB 5EM5

5em5


Resolution: 2.6→24.08 Å / Cor.coef. Fo:Fc: 0.9523 / Cor.coef. Fo:Fc free: 0.9395 / SU R Cruickshank DPI: 0.315 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.3 / SU Rfree Blow DPI: 0.221 / SU Rfree Cruickshank DPI: 0.228
RfactorNum. reflection% reflectionSelection details
Rfree0.2229 665 4.18 %RANDOM
Rwork0.1922 ---
obs0.1935 15892 97.6 %-
Displacement parametersBiso mean: 72.8 Å2
Baniso -1Baniso -2Baniso -3
1-0 Å20 Å20 Å2
2--0 Å20 Å2
3---0 Å2
Refine analyzeLuzzati coordinate error obs: 0.393 Å
Refinement stepCycle: 1 / Resolution: 2.6→24.08 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2389 0 36 7 2432
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0092479HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.093360HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d869SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes57HARMONIC2
X-RAY DIFFRACTIONt_gen_planes345HARMONIC5
X-RAY DIFFRACTIONt_it2479HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion2.79
X-RAY DIFFRACTIONt_other_torsion18.57
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion319SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact2795SEMIHARMONIC4
LS refinement shellResolution: 2.6→2.78 Å / Total num. of bins used: 8
RfactorNum. reflection% reflection
Rfree0.2601 109 3.81 %
Rwork0.227 2753 -
all0.2284 2862 -
obs--97.6 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
12.48620.812-0.89341.2430.24874.80360.0059-0.21550.1273-0.1144-0.0528-0.2252-0.24530.54420.047-0.042-0.10590.0529-0.06530.0378-0.05-55.2797.249-30.411
21.94520.9793-0.58154.4023-0.89911.4815-0.1476-0.1651-0.2862-0.3083-0.1176-0.53130.14630.20740.2652-0.0991-0.01770.0935-0.07980.0654-0.1421-61.428-15.914-22.047
30.15590.3535-0.1940.52760.83770.88630.0018-0.03480.02410.0289-0.0001-0.00150.0012-0.0085-0.00170.1059-0.0878-0.03190.05560.0214-0.0204-65.183.563-6.224
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1{ A|696 - A|786 A|1006 - A|1018 }A696 - 786
2X-RAY DIFFRACTION1{ A|696 - A|786 A|1006 - A|1018 }A1006 - 1018
3X-RAY DIFFRACTION2{ A|787 - A|987 A|1102 - A|1102 }A787 - 987
4X-RAY DIFFRACTION2{ A|787 - A|987 A|1102 - A|1102 }A1102
5X-RAY DIFFRACTION3{ A|988 - A|997 }A988 - 997

+
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