[English] 日本語
Yorodumi
- PDB-2vwu: ephB4 kinase domain inhibitor complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2vwu
TitleephB4 kinase domain inhibitor complex
ComponentsEPHRIN TYPE-B RECEPTOR 4
KeywordsTRANSFERASE / TYROSINE-PROTEIN KINASE / RECEPTOR TYROSINE KINASE / KINASE / MUTANT / MEMBRANE / RECEPTOR / ATP-BINDING / POLYMORPHISM / GLYCOPROTEIN / TRANSMEMBRANE / PHOSPHOPROTEIN / UNPHOSPHORYLATED / NUCLEOTIDE-BINDING
Function / homology
Function and homology information


ephrin receptor activity / cell migration involved in sprouting angiogenesis / EPH-Ephrin signaling / Ephrin signaling / EPH-ephrin mediated repulsion of cells / ephrin receptor signaling pathway / heart morphogenesis / EPHB-mediated forward signaling / transmembrane receptor protein tyrosine kinase activity / receptor protein-tyrosine kinase ...ephrin receptor activity / cell migration involved in sprouting angiogenesis / EPH-Ephrin signaling / Ephrin signaling / EPH-ephrin mediated repulsion of cells / ephrin receptor signaling pathway / heart morphogenesis / EPHB-mediated forward signaling / transmembrane receptor protein tyrosine kinase activity / receptor protein-tyrosine kinase / protein autophosphorylation / angiogenesis / receptor complex / cell adhesion / extracellular exosome / extracellular region / ATP binding / plasma membrane / cytosol
Similarity search - Function
Ephrin type-B receptor 4, ligand binding domain / EPH-B4, SAM domain / Tyrosine-protein kinase ephrin type A/B receptor-like / Tyrosine-protein kinase ephrin type A/B receptor-like / 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-B receptor 4, ligand binding domain / EPH-B4, SAM domain / Tyrosine-protein kinase ephrin type A/B receptor-like / Tyrosine-protein kinase ephrin type A/B receptor-like / 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 / Fibronectin type III domain / Growth factor receptor cysteine-rich domain superfamily / EGF-like domain signature 2. / 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-7X1 / Ephrin type-B receptor 4
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2 Å
AuthorsRead, J. / Brassington, C.A. / Green, I. / McCall, E.J. / Valentine, A.L. / Barratt, D. / Rowsell, S. / Packer, M. / McAlister, M.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2008
Title: Inhibitors of the Tyrosine Kinase Ephb4. Part 1: Structure-Based Design and Optimization of a Series of 2,4-Bis-Anilinopyrimidines
Authors: Bardelle, C. / Cross, D. / Davenport, S. / Kettle, J.G. / Ko, E.J. / Leach, A.G. / Mortlock, A. / Read, J. / Roberts, N.J. / Robins, P. / Williams, E.J.
History
DepositionJun 27, 2008Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jul 8, 2008Provider: repository / Type: Initial release
Revision 1.1May 8, 2011Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Version format compliance
Revision 1.3Apr 3, 2019Group: Data collection / Experimental preparation / Other
Category: exptl_crystal_grow / pdbx_database_proc / pdbx_database_status
Item: _exptl_crystal_grow.temp / _pdbx_database_status.recvd_author_approval
Revision 1.4Apr 24, 2019Group: Data collection / Source and taxonomy / Category: entity_src_gen / Item: _entity_src_gen.pdbx_host_org_cell_line
Revision 1.5May 8, 2019Group: Data collection / Experimental preparation / Category: exptl_crystal_grow / Item: _exptl_crystal_grow.method
Revision 1.6Dec 13, 2023Group: Data collection / Database references ...Data collection / Database references / Other / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: EPHRIN TYPE-B RECEPTOR 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,4062
Polymers33,9351
Non-polymers4711
Water2,288127
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPQS
Unit cell
Length a, b, c (Å)46.490, 53.479, 61.392
Angle α, β, γ (deg.)90.00, 111.15, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein EPHRIN TYPE-B RECEPTOR 4 / EPHB4 RECEPTOR TYROSINE KINASE / TYROSINE-PROTEIN KINASE RECEPTOR HTK / TYROSINE-PROTEIN KINASE TYRO11


Mass: 33934.816 Da / Num. of mol.: 1 / Fragment: KINASE DOMAIN, RESIDUES 598-887 / Mutation: YES
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PFASTBAC / Cell line (production host): Sf21 / Production host: SPODOPTERA FRUGIPERDA (fall armyworm)
References: UniProt: P54760, receptor protein-tyrosine kinase
#2: Chemical ChemComp-7X1 / N-(5-chloro-1,3-benzodioxol-4-yl)-6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-amine


Mass: 470.949 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C24H27ClN4O4
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 127 / Source method: isolated from a natural source / Formula: H2O
Compound detailsENGINEERED RESIDUE IN CHAIN A, TYR 774 TO GLU
Sequence detailsY774E MUTATION NOT SEEN IN ELECTRON DENSITY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.4 Å3/Da / Density % sol: 48.36 % / Description: NONE
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 7.5
Details: PROTEIN: 12MG/ML IN 50MM MOPS PH 6.5, 50MM NACL, 1MM DTT RESERVOIR: 25% PEG 5000 MME, 0.1M TRIS PH 7.5, 0.15M MGCL2, 15% GLYCEROL TEMP: 4 DEGREES C SITTING DROP: 2 UL PROTEIN, 0.6 UL RESERVOIR

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID29 / Wavelength: 0.97568
DetectorType: ADSC CCD / Detector: CCD / Date: Nov 24, 2004 / Details: MIRRORS
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97568 Å / Relative weight: 1
ReflectionResolution: 1.45→56.8 Å / Num. obs: 19173 / % possible obs: 100 % / Observed criterion σ(I): 2 / Redundancy: 7.1 % / Biso Wilson estimate: 16.18 Å2 / Rmerge(I) obs: 0.09 / Net I/σ(I): 5.44
Reflection shellResolution: 2→2.11 Å / Redundancy: 7.15 % / Rmerge(I) obs: 0.38 / Mean I/σ(I) obs: 1.6 / % possible all: 100

-
Processing

Software
NameVersionClassification
REFMAC5.2.0005refinement
MOSFLMdata reduction
SCALAdata scaling
AMoREphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1JPA

1jpa


Resolution: 2→56.8 Å / Cor.coef. Fo:Fc: 0.946 / Cor.coef. Fo:Fc free: 0.935 / SU B: 7.218 / SU ML: 0.094 / Cross valid method: THROUGHOUT / σ(F): 2 / ESU R: 0.17 / ESU R Free: 0.147 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS. THE FOLLOWING RESIDUES ARE DISORDERED 598 TO 608, 649 TO 653, 760 TO 781 AND 888 TO 892
RfactorNum. reflection% reflectionSelection details
Rfree0.209 986 5.16 %RANDOM
Rwork0.175 ---
obs0.177 19159 100 %-
Solvent computationIon probe radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL PLUS MASK
Displacement parametersBiso mean: 23.29 Å2
Baniso -1Baniso -2Baniso -3
1-0.181 Å20 Å2-0.812 Å2
2---0.343 Å20 Å2
3----0.423 Å2
Refinement stepCycle: LAST / Resolution: 2→56.8 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1958 0 33 127 2118
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0110.0222089
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.2951.9792824
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.8735250
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.97523.36895
X-RAY DIFFRACTIONr_dihedral_angle_3_deg11.38615364
X-RAY DIFFRACTIONr_dihedral_angle_4_deg17.1781519
X-RAY DIFFRACTIONr_chiral_restr0.0820.2305
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.022285
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined0.1960.2433
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined0.1830.21041
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1490.288
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.060.25
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.0670.25
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it0.8291.51323
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it1.26722042
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it1.7493920
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it2.7274.5782
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 8.84→56.8 Å / Total num. of bins used: 20 /
RfactorNum. reflection
Rfree0.305 21
Rwork0.289 212

+
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