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

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5nkh
TitleCrystal Structure of Ephrin A2 (EphA2) Receptor Protein Kinase with Compound 3e
ComponentsEphrin type-A receptor 2
KeywordsTRANSFERASE / Inhibitor / Complex / Protein Tyrosine Kinase
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 / positive regulation of bicellular tight junction assembly / regulation of blood vessel endothelial cell migration ...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 / positive regulation of bicellular tight junction assembly / regulation of blood vessel endothelial cell migration / ephrin receptor activity / leading edge membrane / negative regulation of chemokine production / post-anal tail morphogenesis / bone remodeling / response to growth factor / activation of GTPase activity / tight junction / regulation of lamellipodium assembly / branching involved in mammary gland duct morphogenesis / 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 / EPH-ephrin mediated repulsion of cells / ephrin receptor signaling pathway / RAC2 GTPase cycle / RAC3 GTPase cycle / vasculogenesis / regulation of angiogenesis / keratinocyte differentiation / RAC1 GTPase cycle / transmembrane receptor protein tyrosine kinase activity / regulation of ERK1 and ERK2 cascade / negative regulation of angiogenesis / osteoclast differentiation / cell chemotaxis / skeletal system development / molecular function activator activity / protein localization to plasma membrane / cell motility / positive regulation of protein localization to plasma membrane / receptor protein-tyrosine kinase / neuron differentiation / ruffle membrane / intrinsic apoptotic signaling pathway in response to DNA damage / osteoblast differentiation / cell migration / lamellipodium / virus receptor activity / receptor complex / cell adhesion / defense response to Gram-positive bacterium / positive regulation of cell migration / inflammatory response / cadherin binding / 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 / 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. / 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-8ZQ / Ephrin type-A receptor 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.29 Å
AuthorsKudlinzki, D. / Linhard, V.L. / Witt, K. / Gande, S.L. / Saxena, K. / Heinzlmeir, S. / Medard, G. / Kuester, B. / Schwalbe, H.
Funding support Germany, 1items
OrganizationGrant numberCountry
DKTKL590 Germany
CitationJournal: ChemMedChem / Year: 2017
Title: Chemoproteomics-Aided Medicinal Chemistry for the Discovery of EPHA2 Inhibitors.
Authors: Heinzlmeir, S. / Lohse, J. / Treiber, T. / Kudlinzki, D. / Linhard, V. / Gande, S.L. / Sreeramulu, S. / Saxena, K. / Liu, X. / Wilhelm, M. / Schwalbe, H. / Kuster, B. / Medard, G.
History
DepositionMar 31, 2017Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jun 7, 2017Provider: repository / Type: Initial release
Revision 1.1Jun 28, 2017Group: Database references / Category: citation
Item: _citation.country / _citation.journal_volume ..._citation.country / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title
Revision 1.2Jun 12, 2019Group: Data collection / Structure summary
Category: audit_author / database_PDB_rev / database_PDB_rev_record
Item: _audit_author.name
Revision 1.3Aug 14, 2019Group: Data collection / Category: reflns / reflns_shell
Item: _reflns.pdbx_Rrim_I_all / _reflns_shell.number_unique_obs
Revision 1.4Jan 17, 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 / refine_hist
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _refine_hist.d_res_low

-
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)35,0242
Polymers34,4631
Non-polymers5611
Water5,296294
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration, Monomer
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area15350 Å2
MethodPISA
Unit cell
Length a, b, c (Å)32.443, 106.313, 39.325
Angle α, β, γ (deg.)90.00, 94.66, 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 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P29317, receptor protein-tyrosine kinase
#2: Chemical ChemComp-8ZQ / 2-[[3-(2-aminophenyl)-5-(piperidin-4-ylcarbamoyl)phenyl]amino]-~{N}-(2-chloranyl-6-methyl-phenyl)-1,3-thiazole-5-carboxamide


Mass: 561.098 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C29H29ClN6O2S
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 294 / 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: 1.96 Å3/Da / Density % sol: 37.29 %
Crystal growTemperature: 291 K / Method: vapor diffusion, sitting drop / pH: 8.5
Details: 37.5% MPD/PEG1000/PEG3350 (MD), 0.1 M Amino Acids Mix (MD), 0.1 M Buffer System 3 (MD) pH8.5

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: BESSY / Beamline: 14.1 / Wavelength: 0.918409 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jan 23, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.918409 Å / Relative weight: 1
ReflectionResolution: 1.29→32.336 Å / Num. obs: 64198 / % possible obs: 96.3 % / Redundancy: 3.5 % / Biso Wilson estimate: 19.59 Å2 / Rrim(I) all: 0.065 / Net I/σ(I): 11.54
Reflection shellResolution: 1.29→1.37 Å / Mean I/σ(I) obs: 1.82 / Num. unique obs: 6192 / Rrim(I) all: 0.694 / % possible all: 93.7

-
Processing

Software
NameVersionClassification
PHENIX(1.10.1_2155: ???)refinement
XDSXDSapp 2.0data reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5I9U

5i9u


Resolution: 1.29→32.336 Å / SU ML: 0.14 / Cross valid method: FREE R-VALUE / σ(F): 1.37 / Phase error: 20.87
RfactorNum. reflection% reflection
Rfree0.196 2099 3.27 %
Rwork0.17 --
obs0.171 64192 96.3 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Refinement stepCycle: LAST / Resolution: 1.29→32.336 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2343 0 39 294 2676
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0152564
X-RAY DIFFRACTIONf_angle_d1.5263478
X-RAY DIFFRACTIONf_dihedral_angle_d20.4921009
X-RAY DIFFRACTIONf_chiral_restr0.107369
X-RAY DIFFRACTIONf_plane_restr0.009444
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.2889-1.31890.27331330.27573938X-RAY DIFFRACTION92
1.3189-1.35190.26571380.25424101X-RAY DIFFRACTION95
1.3519-1.38850.24971370.24134045X-RAY DIFFRACTION95
1.3885-1.42930.24591380.22274080X-RAY DIFFRACTION95
1.4293-1.47550.25711400.21574116X-RAY DIFFRACTION95
1.4755-1.52820.22521390.20174118X-RAY DIFFRACTION96
1.5282-1.58940.21921390.19294113X-RAY DIFFRACTION96
1.5894-1.66170.22931400.18024152X-RAY DIFFRACTION97
1.6617-1.74930.18561400.17094137X-RAY DIFFRACTION97
1.7493-1.85890.21841420.17084199X-RAY DIFFRACTION97
1.8589-2.00240.19531420.16784183X-RAY DIFFRACTION97
2.0024-2.20390.17771430.15794228X-RAY DIFFRACTION98
2.2039-2.52270.18871420.15784210X-RAY DIFFRACTION98
2.5227-3.17790.18111420.15784203X-RAY DIFFRACTION98
3.1779-32.34580.1731440.14854270X-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