[English] 日本語
Yorodumi
- PDB-5i9x: Crystal Structure of Ephrin A2 (EphA2) Receptor Protein Kinase wi... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5i9x
TitleCrystal Structure of Ephrin A2 (EphA2) Receptor Protein Kinase with bosutinib (SKI-606)
ComponentsEphrin type-A receptor 2
KeywordsTRANSFERASE / TYROSINE-PROTEIN KINASE / RECEPTOR / ATP-BINDING
Function / homology
Function and homology information


notochord cell development / notochord formation / lens fiber cell morphogenesis / blood vessel endothelial cell proliferation involved in sprouting angiogenesis / negative regulation of lymphangiogenesis / axial mesoderm formation / pericyte cell differentiation / cAMP metabolic process / regulation of blood vessel endothelial cell migration / leading edge membrane ...notochord cell development / notochord formation / lens fiber cell morphogenesis / blood vessel endothelial cell proliferation involved in sprouting angiogenesis / negative regulation of lymphangiogenesis / axial mesoderm formation / pericyte cell differentiation / cAMP metabolic process / regulation of blood vessel endothelial cell migration / leading edge membrane / negative regulation of chemokine production / post-anal tail morphogenesis / bone remodeling / response to growth factor / positive regulation of bicellular tight junction assembly / activation of GTPase activity / regulation of lamellipodium assembly / branching involved in mammary gland duct morphogenesis / tight junction / EPH-Ephrin signaling / neural tube development / RND1 GTPase cycle / RND2 GTPase cycle / RND3 GTPase cycle / mammary gland epithelial cell proliferation / RHOV GTPase cycle / EPHA-mediated growth cone collapse / growth factor binding / regulation of cell adhesion mediated by integrin / lamellipodium membrane / RHOU GTPase cycle / RHOG GTPase cycle / ephrin receptor signaling pathway / EPH-ephrin mediated repulsion of cells / RAC2 GTPase cycle / RAC3 GTPase cycle / regulation of angiogenesis / vasculogenesis / regulation of ERK1 and ERK2 cascade / keratinocyte differentiation / transmembrane receptor protein tyrosine kinase activity / RAC1 GTPase cycle / osteoclast differentiation / negative regulation of angiogenesis / molecular function activator activity / skeletal system development / protein localization to plasma membrane / positive regulation of protein localization to plasma membrane / cell chemotaxis / cell motility / placental growth factor receptor activity / insulin receptor activity / 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 / stem cell factor receptor activity / boss receptor activity / protein tyrosine kinase collagen receptor activity / brain-derived neurotrophic factor receptor activity / epidermal growth factor receptor activity / fibroblast growth factor receptor activity / GPI-linked ephrin receptor activity / transmembrane-ephrin receptor activity / insulin-like growth factor receptor activity / receptor protein-tyrosine kinase / neuron differentiation / ruffle membrane / cell surface receptor protein tyrosine kinase signaling pathway / intrinsic apoptotic signaling pathway in response to DNA damage / osteoblast differentiation / cell migration / lamellipodium / virus receptor activity / histone H3Y41 kinase activity / histone H2AXY142 kinase activity / receptor complex / cell adhesion / defense response to Gram-positive bacterium / positive regulation of cell migration / cadherin binding / inflammatory response / focal adhesion / cell surface / ATP binding / plasma membrane
Similarity search - Function
Ephrin type-A receptor 2, ligand binding domain / Ephrin receptor type-A /type-B / Ephrin receptor ligand binding domain / Tyrosine-protein kinase, receptor class V, conserved site / Ephrin receptor, transmembrane domain / : / Ephrin receptor ligand binding domain / Ephrin type-A receptor 2 transmembrane domain / Receptor tyrosine kinase class V signature 1. / Receptor tyrosine kinase class V signature 2. ...Ephrin type-A receptor 2, ligand binding domain / Ephrin receptor type-A /type-B / Ephrin receptor ligand binding domain / Tyrosine-protein kinase, receptor class V, conserved site / Ephrin receptor, transmembrane domain / : / Ephrin receptor ligand binding domain / Ephrin type-A receptor 2 transmembrane domain / Receptor tyrosine kinase class V signature 1. / Receptor tyrosine kinase class V signature 2. / Eph receptor ligand-binding domain profile. / Ephrin receptor ligand binding domain / Putative ephrin-receptor like / SAM domain (Sterile alpha motif) / SAM domain profile. / Sterile alpha motif. / Sterile alpha motif domain / Sterile alpha motif/pointed domain superfamily / Growth factor receptor cysteine-rich domain superfamily / Fibronectin type III domain / Fibronectin type 3 domain / Fibronectin type-III domain profile. / Galactose-binding-like domain superfamily / Fibronectin type III / Fibronectin type III 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. / Immunoglobulin-like fold / 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-DB8 / Ephrin type-A receptor 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.427 Å
AuthorsKudlinzki, D. / Linhard, V.L. / Gande, S.L. / Sreeramulu, S. / Saxena, K. / Heinzlmeir, S. / Medard, G. / Kuester, B. / Schwalbe, H.
Funding support Germany, 1items
OrganizationGrant numberCountry
DKTKL590 Germany
CitationJournal: ACS Chem. Biol. / Year: 2016
Title: Chemical Proteomics and Structural Biology Define EPHA2 Inhibition by Clinical Kinase Drugs.
Authors: Heinzlmeir, S. / Kudlinzki, D. / Sreeramulu, S. / Klaeger, S. / Gande, S.L. / Linhard, V. / Wilhelm, M. / Qiao, H. / Helm, D. / Ruprecht, B. / Saxena, K. / Medard, G. / Schwalbe, H. / Kuster, B.
History
DepositionFeb 21, 2016Deposition site: RCSB / Processing site: PDBE
Revision 1.0Nov 9, 2016Provider: repository / Type: Initial release
Revision 1.1Dec 28, 2016Group: Database references
Revision 1.2Mar 7, 2018Group: Data collection / Source and taxonomy / Category: diffrn_source / entity_src_gen
Item: _diffrn_source.pdbx_synchrotron_site / _entity_src_gen.pdbx_host_org_cell_line / _entity_src_gen.pdbx_host_org_strain
Revision 1.3Jun 12, 2019Group: Data collection / Structure summary
Category: audit_author / database_PDB_rev / database_PDB_rev_record
Item: _audit_author.name
Revision 1.4Jan 10, 2024Group: 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

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Ephrin type-A receptor 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,2426
Polymers34,4631
Non-polymers7795
Water4,234235
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area730 Å2
ΔGint12 kcal/mol
Surface area14520 Å2
MethodPISA
Unit cell
Length a, b, c (Å)32.803, 107.695, 40.604
Angle α, β, γ (deg.)90.00, 108.95, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Ephrin type-A receptor 2 / Epithelial cell kinase / Tyrosine-protein kinase receptor ECK


Mass: 34462.840 Da / Num. of mol.: 1 / Fragment: UNP residues 596-900
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: EPHA2, ECK / Cell line (production host): SF9 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P29317, receptor protein-tyrosine kinase
#2: Chemical ChemComp-DB8 / 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile / Bosutinib


Mass: 530.446 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Formula: C26H29Cl2N5O3 / Details: Ligand ID DB8: bosutinib / Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): Sf9 / Production host: Spodoptera frugiperda (fall armyworm) / References: receptor protein-tyrosine kinase / Comment: inhibitor, medication*YM
#3: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Formula: C2H6O2 / Details: EDO from cryo soaking / Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): Sf9 / Production host: Spodoptera frugiperda (fall armyworm) / References: receptor protein-tyrosine kinase
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 235 / 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: 1.97 Å3/Da / Density % sol: 37.51 %
Crystal growTemperature: 291 K / Method: vapor diffusion, sitting drop
Details: 37.5 % MPD_P1k_P3350, 0.1 M AminoAcidsMix, 0.1 M MES pH 6.0

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: PETRA III, EMBL c/o DESY / Beamline: P13 (MX1) / Wavelength: 1.0332 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jun 15, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.0332 Å / Relative weight: 1
ReflectionResolution: 1.427→38.402 Å / Num. obs: 94778 / % possible obs: 96.8 % / Redundancy: 3.5 % / Net I/σ(I): 12.09
Reflection shellResolution: 1.427→1.51 Å

-
Processing

Software
NameVersionClassification
XDSdata reduction
PHASERphasing
PHENIX(1.10.1_2155: ???)refinement
Cootmodel building
XDSdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1MQB

1mqb


Resolution: 1.427→38.402 Å / SU ML: 0.13 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 17.52
RfactorNum. reflection% reflection
Rfree0.182 4745 5.01 %
Rwork0.165 --
obs0.1659 94776 96.97 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Refinement stepCycle: LAST / Resolution: 1.427→38.402 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2268 0 52 235 2555
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0062410
X-RAY DIFFRACTIONf_angle_d0.8773250
X-RAY DIFFRACTIONf_dihedral_angle_d21.065923
X-RAY DIFFRACTIONf_chiral_restr0.082346
X-RAY DIFFRACTIONf_plane_restr0.005410
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.427-1.44320.28711430.27382649X-RAY DIFFRACTION86
1.4432-1.46020.25611510.24742893X-RAY DIFFRACTION95
1.4602-1.4780.26731600.22923026X-RAY DIFFRACTION96
1.478-1.49670.24741560.23612987X-RAY DIFFRACTION96
1.4967-1.51640.2211560.22692955X-RAY DIFFRACTION96
1.5164-1.53720.2751580.21742992X-RAY DIFFRACTION96
1.5372-1.55920.20541550.222978X-RAY DIFFRACTION96
1.5592-1.58240.23271550.20072966X-RAY DIFFRACTION97
1.5824-1.60720.19211560.19722976X-RAY DIFFRACTION97
1.6072-1.63350.18161610.19743030X-RAY DIFFRACTION97
1.6335-1.66170.1691560.19052932X-RAY DIFFRACTION95
1.6617-1.69190.18131550.18632962X-RAY DIFFRACTION97
1.6919-1.72440.21181640.18063049X-RAY DIFFRACTION97
1.7244-1.75960.20951560.17262960X-RAY DIFFRACTION97
1.7596-1.79790.17311580.15863004X-RAY DIFFRACTION97
1.7979-1.83970.1591610.15883063X-RAY DIFFRACTION98
1.8397-1.88570.15561570.15662962X-RAY DIFFRACTION98
1.8857-1.93670.17161630.15273113X-RAY DIFFRACTION98
1.9367-1.99370.1741550.15322958X-RAY DIFFRACTION98
1.9937-2.0580.16221620.15213088X-RAY DIFFRACTION97
2.058-2.13160.19731600.14963044X-RAY DIFFRACTION98
2.1316-2.21690.16151590.153017X-RAY DIFFRACTION99
2.2169-2.31780.19511590.15383053X-RAY DIFFRACTION98
2.3178-2.440.19491590.15493038X-RAY DIFFRACTION99
2.44-2.59280.17171630.15443065X-RAY DIFFRACTION99
2.5928-2.7930.17491610.15943032X-RAY DIFFRACTION98
2.793-3.07390.17991630.15213067X-RAY DIFFRACTION98
3.0739-3.51850.1691570.1483059X-RAY DIFFRACTION99
3.5185-4.43190.1461620.14093059X-RAY DIFFRACTION99
4.4319-38.41610.18471640.1733054X-RAY DIFFRACTION98

+
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