[English] 日本語
Yorodumi
- PDB-6fnh: Crystal Structure of Ephrin A2 (EphA2) Receptor Protein Kinase wi... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6fnh
TitleCrystal Structure of Ephrin A2 (EphA2) Receptor Protein Kinase with a pyrazolo[3,4-d]pyrimidine fragment of NVP-BHG712
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 / 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 / response to growth factor / bone remodeling / positive regulation of bicellular tight junction assembly / regulation of lamellipodium assembly / activation of GTPase activity / branching involved in mammary gland duct morphogenesis / tight junction / EPH-Ephrin signaling / RND1 GTPase cycle / neural tube development / 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 / regulation of angiogenesis / regulation of ERK1 and ERK2 cascade / vasculogenesis / keratinocyte differentiation / transmembrane receptor protein tyrosine kinase activity / RAC1 GTPase cycle / osteoclast differentiation / cell surface receptor protein tyrosine kinase signaling pathway / negative regulation of angiogenesis / molecular function activator activity / protein localization to plasma membrane / skeletal system development / cell chemotaxis / positive regulation of protein localization to plasma membrane / 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 / transmembrane-ephrin receptor activity / GPI-linked ephrin receptor activity / epidermal growth factor receptor activity / fibroblast growth factor receptor activity / insulin-like growth factor receptor activity / receptor protein-tyrosine kinase / ruffle membrane / intrinsic apoptotic signaling pathway in response to DNA damage / neuron differentiation / osteoblast differentiation / cell migration / lamellipodium / virus receptor activity / angiogenesis / receptor complex / defense response to Gram-positive bacterium / cell adhesion / 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-DXK / Ephrin type-A receptor 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.379 Å
AuthorsKudlinzki, D. / Troester, A. / Witt, K. / Linhard, V.L. / Gande, S.L. / Saxena, K. / Schwalbe, H.
Funding support Germany, 1items
OrganizationGrant numberCountry
DKTKL590 Germany
CitationJournal: ChemMedChem / Year: 2018
Title: NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family.
Authors: Troster, A. / Heinzlmeir, S. / Berger, B.T. / Gande, S.L. / Saxena, K. / Sreeramulu, S. / Linhard, V. / Nasiri, A.H. / Bolte, M. / Muller, S. / Kuster, B. / Medard, G. / Kudlinzki, D. / Schwalbe, H.
History
DepositionFeb 4, 2018Deposition site: PDBE / Processing site: PDBE
Revision 1.0Aug 8, 2018Provider: repository / Type: Initial release
Revision 1.1Aug 29, 2018Group: Data collection / Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.2Jan 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
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
B: Ephrin type-A receptor 2
C: Ephrin type-A receptor 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)105,12223
Polymers103,3893
Non-polymers1,73420
Water11,638646
1
A: Ephrin type-A receptor 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,37213
Polymers34,4631
Non-polymers90912
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Ephrin type-A receptor 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,9376
Polymers34,4631
Non-polymers4755
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
C: Ephrin type-A receptor 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,8134
Polymers34,4631
Non-polymers3503
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)56.500, 90.674, 200.316
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

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


Mass: 34462.840 Da / Num. of mol.: 3
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-DXK / 1-methyl-6-pyridin-3-yl-pyrazolo[3,4-d]pyrimidin-4-amine


Mass: 226.237 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C11H10N6
#3: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 17 / Source method: obtained synthetically / Formula: C2H6O2
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 646 / 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: 2.75 Å3/Da / Density % sol: 55.32 %
Crystal growTemperature: 291 K / Method: vapor diffusion, sitting drop / pH: 8.5
Details: 37.5 % MPD/PEG1000/PEG3350 (MD), 0.075 M Carboxylic Acids Mix (MD), 0.1 M Buffer System 3 (MD) pH 8.5

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: PETRA III, EMBL c/o DESY / Beamline: P13 (MX1) / Wavelength: 1.03318 Å
DetectorType: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Sep 15, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.03318 Å / Relative weight: 1
ReflectionResolution: 1.379→49.21 Å / Num. obs: 212089 / % possible obs: 99.6 % / Redundancy: 13.03 % / Biso Wilson estimate: 34.78 Å2 / CC1/2: 0.999 / Rrim(I) all: 0.095 / Net I/σ(I): 10.57
Reflection shellResolution: 1.379→1.46 Å / Redundancy: 12.67 % / Mean I/σ(I) obs: 0.22 / Num. unique obs: 33386 / CC1/2: 0.109 / % possible all: 98

-
Processing

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

5i9u


Resolution: 1.379→47.953 Å / SU ML: 0.31 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 37.38
RfactorNum. reflection% reflection
Rfree0.2212 2216 1.05 %
Rwork0.2057 --
obs0.2056 210857 99.39 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Refinement stepCycle: LAST / Resolution: 1.379→47.953 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6526 0 119 647 7292
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0086862
X-RAY DIFFRACTIONf_angle_d0.9589226
X-RAY DIFFRACTIONf_dihedral_angle_d18.4974132
X-RAY DIFFRACTIONf_chiral_restr0.085994
X-RAY DIFFRACTIONf_plane_restr0.0071161
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.3786-1.40860.6151280.600412069X-RAY DIFFRACTION93
1.4086-1.44140.56181370.581412844X-RAY DIFFRACTION99
1.4414-1.47740.50321370.555812957X-RAY DIFFRACTION100
1.4774-1.51740.4851380.502913003X-RAY DIFFRACTION100
1.5174-1.5620.41931380.435512993X-RAY DIFFRACTION100
1.562-1.61250.36321380.380213018X-RAY DIFFRACTION100
1.6125-1.67010.32231390.332613021X-RAY DIFFRACTION100
1.6701-1.7370.33111370.298412954X-RAY DIFFRACTION100
1.737-1.8160.30281390.272113100X-RAY DIFFRACTION100
1.816-1.91180.25481390.221613020X-RAY DIFFRACTION100
1.9118-2.03160.23491390.208413088X-RAY DIFFRACTION100
2.0316-2.18840.23371390.200213134X-RAY DIFFRACTION100
2.1884-2.40860.19941400.197413149X-RAY DIFFRACTION100
2.4086-2.75710.2271400.201113209X-RAY DIFFRACTION100
2.7571-3.47360.22211410.185713328X-RAY DIFFRACTION100
3.4736-47.98160.17151470.160313754X-RAY DIFFRACTION100

+
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