[English] 日本語
Yorodumi
- PDB-5ew3: Human Vascular Endothelial Growth Factor Receptor 2 (KDR) Kinase ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5ew3
TitleHuman Vascular Endothelial Growth Factor Receptor 2 (KDR) Kinase Domain in complex with AAL993
ComponentsVascular endothelial growth factor receptor 2
KeywordsTRANSFERASE / kdr / kinase domain / ATP-binding site / VEGFR2 inhibitors
Function / homology
Function and homology information


positive regulation of nitric oxide-cGMP mediated signal transduction / blood vessel endothelial cell differentiation / regulation of bone development / cellular response to hydrogen sulfide / Signaling by membrane-tethered fusions of PDGFRA or PDGFRB / Neurophilin interactions with VEGF and VEGFR / vascular endothelial growth factor binding / vascular endothelial growth factor receptor-2 signaling pathway / endothelium development / VEGF binds to VEGFR leading to receptor dimerization ...positive regulation of nitric oxide-cGMP mediated signal transduction / blood vessel endothelial cell differentiation / regulation of bone development / cellular response to hydrogen sulfide / Signaling by membrane-tethered fusions of PDGFRA or PDGFRB / Neurophilin interactions with VEGF and VEGFR / vascular endothelial growth factor binding / vascular endothelial growth factor receptor-2 signaling pathway / endothelium development / VEGF binds to VEGFR leading to receptor dimerization / endocardium development / vascular wound healing / vascular endothelial growth factor receptor activity / endothelial cell differentiation / regulation of hematopoietic progenitor cell differentiation / post-embryonic camera-type eye morphogenesis / lymph vessel development / mesenchymal cell proliferation / positive regulation of vasculogenesis / positive regulation of BMP signaling pathway / surfactant homeostasis / cell migration involved in sprouting angiogenesis / epithelial cell maturation / positive regulation of positive chemotaxis / positive regulation of endothelial cell chemotaxis / positive regulation of cell migration involved in sprouting angiogenesis / embryonic hemopoiesis / positive regulation of mesenchymal cell proliferation / anchoring junction / vascular endothelial growth factor signaling pathway / lung alveolus development / growth factor binding / positive regulation of mitochondrial fission / branching involved in blood vessel morphogenesis / positive regulation of stem cell proliferation / positive regulation of mitochondrial depolarization / sorting endosome / semaphorin-plexin signaling pathway / regulation of MAPK cascade / positive regulation of macroautophagy / cellular response to vascular endothelial growth factor stimulus / positive regulation of blood vessel endothelial cell migration / positive regulation of focal adhesion assembly / cell fate commitment / vascular endothelial growth factor receptor signaling pathway / Integrin cell surface interactions / negative regulation of endothelial cell apoptotic process / vasculogenesis / calcium ion homeostasis / ovarian follicle development / coreceptor activity / positive regulation of endothelial cell proliferation / transmembrane receptor protein tyrosine kinase activity / positive regulation of endothelial cell migration / cell surface receptor protein tyrosine kinase signaling pathway / peptidyl-tyrosine phosphorylation / VEGFR2 mediated cell proliferation / epithelial cell proliferation / stem cell proliferation / Hsp90 protein binding / receptor protein-tyrosine kinase / VEGFA-VEGFR2 Pathway / integrin binding / positive regulation of protein phosphorylation / positive regulation of angiogenesis / cell junction / cell migration / regulation of cell shape / protein autophosphorylation / protein tyrosine kinase activity / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / angiogenesis / negative regulation of neuron apoptotic process / early endosome / positive regulation of ERK1 and ERK2 cascade / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor complex / endosome / positive regulation of MAPK cascade / positive regulation of cell migration / cadherin binding / membrane raft / negative regulation of gene expression / external side of plasma membrane / positive regulation of cell population proliferation / endoplasmic reticulum / Golgi apparatus / extracellular region / ATP binding / identical protein binding / nucleus / plasma membrane
Similarity search - Function
Vascular endothelial growth factor receptor 2 (VEGFR2) / VEGFR-2, transmembrane domain / : / : / VEGFR-2 Transmembrane domain / Vascular endothelial growth factor receptor 1-like, Ig-like domain / VEGFR1-3, N-terminal Ig-like domain / VEGFR-1-like, immunoglobulin-like domain / Tyrosine-protein kinase, receptor class III, conserved site / Receptor tyrosine kinase class III signature. ...Vascular endothelial growth factor receptor 2 (VEGFR2) / VEGFR-2, transmembrane domain / : / : / VEGFR-2 Transmembrane domain / Vascular endothelial growth factor receptor 1-like, Ig-like domain / VEGFR1-3, N-terminal Ig-like domain / VEGFR-1-like, immunoglobulin-like domain / Tyrosine-protein kinase, receptor class III, conserved site / Receptor tyrosine kinase class III signature. / Immunoglobulin domain / Immunoglobulin / Immunoglobulin domain / Immunoglobulin I-set / Immunoglobulin I-set domain / : / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Immunoglobulin subtype / Immunoglobulin / 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 / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / 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-5T2 / Vascular endothelial growth factor receptor 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.5 Å
AuthorsStark, W. / Goepfert, A.
Citation
Journal: J.Med.Chem. / Year: 2016
Title: A Novel Potent Oral Series of VEGFR2 Inhibitors Abrogate Tumor Growth by Inhibiting Angiogenesis.
Authors: Bold, G. / Schnell, C. / Furet, P. / McSheehy, P. / Bruggen, J. / Mestan, J. / Manley, P.W. / Druckes, P. / Burglin, M. / Durler, U. / Loretan, J. / Reuter, R. / Wartmann, M. / Theuer, A. / ...Authors: Bold, G. / Schnell, C. / Furet, P. / McSheehy, P. / Bruggen, J. / Mestan, J. / Manley, P.W. / Druckes, P. / Burglin, M. / Durler, U. / Loretan, J. / Reuter, R. / Wartmann, M. / Theuer, A. / Bauer-Probst, B. / Martiny-Baron, G. / Allegrini, P. / Goepfert, A. / Wood, J. / Littlewood-Evans, A.
#1: Journal: Biochimica et Biophysica Acta, Proteins and Proteomics
Year: 2004
Title: Advances in the structural biology, design and clinical development of VEGF-R kinase inhibitors for the treatment of angiogenesis
Authors: Manley, P.W. / Bold, G. / Bruggen, J. / Fendrich, G. / Furet, P. / Mestan, J. / Schnell, C. / Stolz, B. / Meyer, T. / Meyhack, B. / Stark, W. / Strauss, A. / Wood, J.
History
DepositionNov 20, 2015Deposition site: RCSB / Processing site: PDBE
Revision 1.0Dec 16, 2015Provider: repository / Type: Initial release
Revision 1.1Jan 27, 2016Group: Database references
Revision 1.2Jan 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: Vascular endothelial growth factor receptor 2
B: Vascular endothelial growth factor receptor 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)73,1324
Polymers72,3902
Non-polymers7432
Water1,36976
1
A: Vascular endothelial growth factor receptor 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,5662
Polymers36,1951
Non-polymers3711
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Vascular endothelial growth factor receptor 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,5662
Polymers36,1951
Non-polymers3711
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)67.500, 55.760, 89.760
Angle α, β, γ (deg.)90.000, 92.280, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Vascular endothelial growth factor receptor 2 / VEGFR-2 / Fetal liver kinase 1 / FLK-1 / Kinase insert domain receptor / KDR / Protein-tyrosine ...VEGFR-2 / Fetal liver kinase 1 / FLK-1 / Kinase insert domain receptor / KDR / Protein-tyrosine kinase receptor flk-1


Mass: 36194.762 Da / Num. of mol.: 2 / Fragment: kinase domain, residues 806-1171 / Mutation: E990V
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KDR, FLK1, VEGFR2 / Plasmid: pVL1393 / Cell line (production host): SF9 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P35968, receptor protein-tyrosine kinase
#2: Chemical ChemComp-5T2 / 2-(pyridin-4-ylmethylamino)-~{N}-[3-(trifluoromethyl)phenyl]benzamide


Mass: 371.356 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C20H16F3N3O
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 76 / 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: 2.33 Å3/Da / Density % sol: 47.25 %
Crystal growTemperature: 290 K / Method: vapor diffusion, hanging drop / pH: 6.5
Details: 0.1M MES pH6.5, 8% w/v PEG 8000, 0.02M LITHIUM ACETATE

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 0.8727 Å
DetectorType: MAR scanner 345 mm plate / Detector: IMAGE PLATE / Date: Oct 3, 2002
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.8727 Å / Relative weight: 1
ReflectionResolution: 2.5→100 Å / Num. all: 23547 / Num. obs: 23229 / % possible obs: 98.9 % / Redundancy: 3.37 % / Rmerge(I) obs: 0.081 / Net I/σ(I): 17.05
Reflection shellResolution: 2.5→2.59 Å / Rmerge(I) obs: 0.582 / % possible all: 98.9

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassification
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing
BUSTER-TNTrefinement
PDB_EXTRACT3.15data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1vr2

1vr2


Resolution: 2.5→19.68 Å / Cor.coef. Fo:Fc: 0.9287 / Cor.coef. Fo:Fc free: 0.9109 / SU R Cruickshank DPI: 0.503 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.473 / SU Rfree Blow DPI: 0.271 / SU Rfree Cruickshank DPI: 0.278
RfactorNum. reflection% reflectionSelection details
Rfree0.2535 665 2.88 %RANDOM
Rwork0.2184 ---
obs0.2194 23051 98.94 %-
Displacement parametersBiso max: 167.08 Å2 / Biso mean: 62.95 Å2 / Biso min: 27.07 Å2
Baniso -1Baniso -2Baniso -3
1--0.4887 Å20 Å20.1703 Å2
2---1.5698 Å20 Å2
3---2.0584 Å2
Refinement stepCycle: final / Resolution: 2.5→19.68 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4324 0 54 76 4454
Biso mean--45.79 56.14 -
Num. residues----540
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d1559SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes90HARMONIC2
X-RAY DIFFRACTIONt_gen_planes645HARMONIC5
X-RAY DIFFRACTIONt_it4486HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion559SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact4891SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d4486HARMONIC20.008
X-RAY DIFFRACTIONt_angle_deg6057HARMONIC20.99
X-RAY DIFFRACTIONt_omega_torsion2.51
X-RAY DIFFRACTIONt_other_torsion15.75
LS refinement shellResolution: 2.5→2.61 Å / Total num. of bins used: 12
RfactorNum. reflection% reflection
Rfree0.2653 90 3.27 %
Rwork0.2179 2666 -
all0.2193 2756 -
obs--98.94 %

+
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