[English] 日本語
Yorodumi
- PDB-3lzb: EGFR kinase domain complexed with an imidazo[2,1-b]thiazole inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3lzb
TitleEGFR kinase domain complexed with an imidazo[2,1-b]thiazole inhibitor
ComponentsEpidermal growth factor receptor
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / epidermal growth factor kinase domain / multitargeted small molecule kinase inhibitor / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


response to hydroxyisoflavone / multivesicular body, internal vesicle lumen / positive regulation of prolactin secretion / negative regulation of cardiocyte differentiation / positive regulation of protein kinase C activity / 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 prolactin secretion / negative regulation of cardiocyte differentiation / positive regulation of protein kinase C activity / 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 / response to UV-A / epidermal growth factor binding / PLCG1 events in ERBB2 signaling / tongue development / midgut development / ERBB2-EGFR signaling pathway / hydrogen peroxide metabolic process / PTK6 promotes HIF1A stabilization / digestive tract morphogenesis / regulation of nitric-oxide synthase activity / ERBB2 Activates PTK6 Signaling / morphogenesis of an epithelial fold / intracellular vesicle / Signaling by EGFR / response to cobalamin / negative regulation of epidermal growth factor receptor signaling pathway / transmembrane receptor protein tyrosine kinase activator activity / protein tyrosine kinase activator activity / Signaling by ERBB4 / regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / protein insertion into membrane / eyelid development in camera-type eye / cerebral cortex cell migration / ERBB2 Regulates Cell Motility / regulation of JNK cascade / activation of phospholipase C activity / positive regulation of cyclin-dependent protein serine/threonine kinase activity / PI3K events in ERBB2 signaling / negative regulation of mitotic cell cycle / hair follicle development / MAP kinase kinase kinase activity / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / positive regulation of G1/S transition of mitotic cell cycle / embryonic placenta development / positive regulation of bone resorption / GAB1 signalosome / positive regulation of nitric oxide mediated signal transduction / salivary gland morphogenesis / regulation of peptidyl-tyrosine phosphorylation / peptidyl-tyrosine autophosphorylation / positive regulation of glial cell proliferation / positive regulation of phosphorylation / positive regulation of vasoconstriction / Signaling by ERBB2 / cellular response to epidermal growth factor stimulus / cellular response to cadmium ion / positive regulation of DNA repair / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / EGFR Transactivation by Gastrin / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / GRB2 events in ERBB2 signaling / transmembrane receptor protein tyrosine kinase activity / neurogenesis / cellular response to dexamethasone stimulus / SHC1 events in ERBB2 signaling / ossification / positive regulation of synaptic transmission, glutamatergic / basal plasma membrane / regulation of ERK1 and ERK2 cascade / neuron projection morphogenesis / positive regulation of superoxide anion generation / positive regulation of DNA replication / Signal transduction by L1 / epithelial cell proliferation / cellular response to estradiol stimulus / liver regeneration / positive regulation of epithelial cell proliferation / NOTCH3 Activation and Transmission of Signal to the Nucleus / astrocyte activation / cellular response to amino acid stimulus / positive regulation of protein localization to plasma membrane / EGFR downregulation / clathrin-coated endocytic vesicle membrane / positive regulation of smooth muscle cell proliferation / lung development / Signaling by ERBB2 TMD/JMD mutants / Constitutive Signaling by EGFRvIII / positive regulation of MAP kinase activity / Signaling by ERBB2 ECD mutants / epidermal growth factor receptor signaling pathway / Signaling by ERBB2 KD Mutants / negative regulation of protein catabolic process / cell-cell adhesion / receptor protein-tyrosine kinase / ruffle membrane / Downregulation of ERBB2 signaling / cellular response to reactive oxygen species
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 / 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 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-ITI / Epidermal growth factor receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.7 Å
AuthorsSwinger, K.K.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2010
Title: Imidazo[2,1-b]thiazoles: multitargeted inhibitors of both the insulin-like growth factor receptor and members of the epidermal growth factor family of receptor tyrosine kinases.
Authors: Fidanze, S.D. / Erickson, S.A. / Wang, G.T. / Mantei, R. / Clark, R.F. / Sorensen, B.K. / Bamaung, N.Y. / Kovar, P. / Johnson, E.F. / Swinger, K.K. / Stewart, K.D. / Zhang, Q. / Tucker, L.A. ...Authors: Fidanze, S.D. / Erickson, S.A. / Wang, G.T. / Mantei, R. / Clark, R.F. / Sorensen, B.K. / Bamaung, N.Y. / Kovar, P. / Johnson, E.F. / Swinger, K.K. / Stewart, K.D. / Zhang, Q. / Tucker, L.A. / Pappano, W.N. / Wilsbacher, J.L. / Wang, J. / Sheppard, G.S. / Bell, R.L. / Davidsen, S.K. / Hubbard, R.D.
History
DepositionMar 1, 2010Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 2, 2011Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Oct 13, 2021Group: Database references / Derived calculations / Category: database_2 / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.3Sep 6, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
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
E: Epidermal growth factor receptor
F: Epidermal growth factor receptor
G: Epidermal growth factor receptor
H: Epidermal growth factor receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)291,45112
Polymers289,1008
Non-polymers2,3514
Water2,738152
1
A: Epidermal growth factor receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,7252
Polymers36,1371
Non-polymers5881
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Epidermal growth factor receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,7252
Polymers36,1371
Non-polymers5881
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
3
C: Epidermal growth factor receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,7252
Polymers36,1371
Non-polymers5881
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
4
D: Epidermal growth factor receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,7252
Polymers36,1371
Non-polymers5881
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
5
E: Epidermal growth factor receptor


  • defined by author&software
  • 36.1 kDa, 1 polymers
Theoretical massNumber of molelcules
Total (without water)36,1371
Polymers36,1371
Non-polymers00
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
6
F: Epidermal growth factor receptor


  • defined by author&software
  • 36.1 kDa, 1 polymers
Theoretical massNumber of molelcules
Total (without water)36,1371
Polymers36,1371
Non-polymers00
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
7
G: Epidermal growth factor receptor


  • defined by author&software
  • 36.1 kDa, 1 polymers
Theoretical massNumber of molelcules
Total (without water)36,1371
Polymers36,1371
Non-polymers00
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
8
H: Epidermal growth factor receptor


  • defined by author&software
  • 36.1 kDa, 1 polymers
Theoretical massNumber of molelcules
Total (without water)36,1371
Polymers36,1371
Non-polymers00
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)85.586, 70.874, 115.182
Angle α, β, γ (deg.)90.00, 109.36, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

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


Mass: 36137.484 Da / Num. of mol.: 8 / Fragment: UNP residues 696-1022 / Mutation: V924R
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: EGFR, ERBB1 / Production host: Spodoptera frugiperda (fall armyworm) / Strain (production host): Hi5
References: UniProt: P00533, receptor protein-tyrosine kinase
#2: Chemical
ChemComp-ITI / N-[3-(5-{2-[(4-morpholin-4-ylphenyl)amino]pyrimidin-4-yl}imidazo[2,1-b][1,3]thiazol-6-yl)phenyl]-2-phenylacetamide


Mass: 587.694 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C33H29N7O2S
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 152 / Source method: isolated from a natural source / Formula: H2O
Sequence detailsTHE ACTUAL CRYSTALLIZED SEQUENCE FOR THE LAST 39 C-TERMINAL RESIDUES IS ...THE ACTUAL CRYSTALLIZED SEQUENCE FOR THE LAST 39 C-TERMINAL RESIDUES IS DERMHLPSPTDSNFYRALMDEEDMDDVVDADEYLIPQQG, CORRESPONDING TO THE UNP RESIDUES P00533:983-022. THESE RESIDUES WERE MODELED AS ALA IN CHAINS E,F,G,H AND WERE CHANGED TO UNK SINCE THE AUTHORS DO NOT KNOW THE CORRESPONDENCE BETWEEN THE SEQUENCE AND COORDINATES IN THIS REGION OF THE CHAINS.

-
Experimental details

-
Experiment

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

-
Sample preparation

Crystal growTemperature: 290 K / Method: vapor diffusion, sitting drop / pH: 7.7
Details: 0.15M cesium chloride, 15% w/v polyethylene glycol 3350, pH 7.7, VAPOR DIFFUSION, SITTING DROP, temperature 290K

-
Data collection

DiffractionMean temperature: 77 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-BM / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 210 / Detector: CCD / Date: Jun 3, 2009 / Details: mirrors
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.7→50 Å / Num. all: 36061 / Num. obs: 36046 / % possible obs: 99.8 % / Redundancy: 3.7 % / Biso Wilson estimate: 62.974 Å2 / Rmerge(I) obs: 0.131 / Rsym value: 0.131 / Net I/σ(I): 13.55
Reflection shellResolution: 2.7→2.8 Å / Redundancy: 3.6 % / Rmerge(I) obs: 0.52 / Mean I/σ(I) obs: 2.1 / Num. unique all: 3571 / Rsym value: 0.52 / % possible all: 76

-
Processing

Software
NameVersionClassification
MAR345dtbdata collection
PHASERphasing
BUSTER-TNT2.5.1refinement
HKL-2000data reduction
HKL-2000data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 2GS7

2gs7


Resolution: 2.7→44.17 Å / Cross valid method: THROUGHOUT / σ(F): 2.7 / σ(I): 2.7
RfactorNum. reflection% reflectionSelection details
Rfree0.2574 1801 5 %RANDOM
Rwork0.2037 ---
obs0.2064 36046 99.54 %-
all-36061 --
Displacement parametersBiso mean: 57.9 Å2
Baniso -1Baniso -2Baniso -3
1-11.6792929 Å20 Å220.33935063 Å2
2--1.40290831 Å20 Å2
3----13.08220121 Å2
Refinement stepCycle: LAST / Resolution: 2.7→44.17 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8561 0 172 152 8885
Refine LS restraints
Refine-IDTypeDev idealNumberWeight
X-RAY DIFFRACTIONt_bond_d0.01189372
X-RAY DIFFRACTIONt_angle_deg1.326120542
X-RAY DIFFRACTIONt_dihedral_angle_d25.26817630
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes0.011742
X-RAY DIFFRACTIONt_gen_planes0.01513365
X-RAY DIFFRACTIONt_it2.087874120
X-RAY DIFFRACTIONt_nbd0.0671665
LS refinement shellResolution: 2.7→2.8 Å / Total num. of bins used: 9
RfactorNum. reflection% reflection
Rfree0.2792 274 4.79 %
Rwork0.2208 5444 -
all0.2237 5718 -
obs-5718 99.54 %

+
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