[English] 日本語
Yorodumi
- PDB-4agd: CRYSTAL STRUCTURE OF VEGFR2 (JUXTAMEMBRANE AND KINASE DOMAINS) IN... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4agd
TitleCRYSTAL STRUCTURE OF VEGFR2 (JUXTAMEMBRANE AND KINASE DOMAINS) IN COMPLEX WITH SUNITINIB (SU11248) (N-2-diethylaminoethyl)-5-((Z)-(5- fluoro-2-oxo-1H-indol-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3- carboxamide)
ComponentsVASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR 2
KeywordsTRANSFERASE / ANGIOGENESIS / NUCLEOTIDE-BINDING / INHIBITOR / PHOSPHORYLATION / TRANSMEMBRANE
Function / homology
Function and homology information


blood vessel endothelial cell differentiation / cellular response to hydrogen sulfide / regulation of bone development / 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 ...blood vessel endothelial cell differentiation / cellular response to hydrogen sulfide / regulation of bone development / 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 / regulation of hematopoietic progenitor cell differentiation / post-embryonic camera-type eye morphogenesis / lymph vessel development / positive regulation of vasculogenesis / mesenchymal cell proliferation / endothelial cell differentiation / positive regulation of BMP signaling pathway / surfactant homeostasis / cell migration involved in sprouting angiogenesis / epithelial cell maturation / positive regulation of positive chemotaxis / embryonic hemopoiesis / positive regulation of endothelial cell chemotaxis / anchoring junction / vascular endothelial growth factor signaling pathway / positive regulation of mesenchymal cell proliferation / positive regulation of cell migration involved in sprouting angiogenesis / positive regulation of mitochondrial fission / branching involved in blood vessel morphogenesis / lung alveolus development / positive regulation of mitochondrial depolarization / positive regulation of stem cell proliferation / growth factor binding / : / sorting endosome / positive regulation of macroautophagy / semaphorin-plexin signaling pathway / regulation of MAPK cascade / cellular response to vascular endothelial growth factor stimulus / positive regulation of focal adhesion assembly / positive regulation of blood vessel endothelial cell migration / cell fate commitment / Integrin cell surface interactions / vascular endothelial growth factor receptor signaling pathway / vasculogenesis / negative regulation of endothelial cell apoptotic process / peptidyl-tyrosine autophosphorylation / calcium ion homeostasis / coreceptor activity / ovarian follicle development / transmembrane receptor protein tyrosine kinase activity / positive regulation of endothelial cell proliferation / positive regulation of endothelial cell migration / VEGFR2 mediated cell proliferation / epithelial cell proliferation / stem cell proliferation / Hsp90 protein binding / 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 / GPI-linked ephrin receptor activity / transmembrane-ephrin receptor activity / epidermal growth factor receptor activity / fibroblast growth factor receptor activity / insulin-like growth factor receptor activity / receptor protein-tyrosine kinase / peptidyl-tyrosine phosphorylation / VEGFA-VEGFR2 Pathway / cell surface receptor protein tyrosine kinase signaling pathway / positive regulation of angiogenesis / cell migration / integrin binding / cell junction / regulation of cell shape / protein tyrosine kinase activity / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / protein autophosphorylation / angiogenesis / histone H3Y41 kinase activity / histone H2AXY142 kinase activity / negative regulation of neuron apoptotic process / positive regulation of MAPK cascade / positive regulation of ERK1 and ERK2 cascade / positive regulation of protein phosphorylation / early endosome / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor complex / endosome / positive regulation of cell migration / cadherin binding / membrane raft
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 / Ig-like domain profile. / Immunoglobulin-like domain / Phosphorylase Kinase; domain 1 / Immunoglobulin-like domain superfamily / 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-B49 / Vascular endothelial growth factor receptor 2
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.81 Å
AuthorsMcTigue, M. / Deng, Y. / Ryan, K. / Brooun, A. / Diehl, W. / Stewart, A.
CitationJournal: Proc.Natl.Acad.Sci.USA / Year: 2012
Title: Molecular Conformations, Interactions, and Properties Associated with Drug Efficiency and Clinical Performance Among Vegfr Tk Inhibitors.
Authors: Mctigue, M. / Murray, B.W. / Chen, J.H. / Deng, Y. / Solowiej, J. / Kania, R.S.
History
DepositionJan 26, 2012Deposition site: PDBE / Processing site: PDBE
Revision 1.0Sep 26, 2012Provider: repository / Type: Initial release
Revision 1.1Nov 14, 2012Group: Database references
Revision 1.2May 8, 2019Group: Data collection / Experimental preparation / Other
Category: database_PDB_rev / database_PDB_rev_record ...database_PDB_rev / database_PDB_rev_record / exptl_crystal_grow / pdbx_database_proc / pdbx_database_status
Item: _exptl_crystal_grow.method / _exptl_crystal_grow.temp / _pdbx_database_status.recvd_author_approval
Revision 1.3Dec 20, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Refinement description / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / entity / pdbx_database_status / pdbx_entity_nonpoly / pdbx_initial_refinement_model / struct_site
Item: _chem_comp.name / _database_2.pdbx_DOI ..._chem_comp.name / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _entity.pdbx_description / _pdbx_database_status.status_code_sf / _pdbx_entity_nonpoly.name / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)40,6572
Polymers40,2581
Non-polymers3981
Water1,56787
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)134.694, 56.980, 52.720
Angle α, β, γ (deg.)90.00, 94.34, 90.00
Int Tables number5
Space group name H-MC121

-
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 / CD309


Mass: 40258.391 Da / Num. of mol.: 1
Fragment: JUXTAMEMBRANE AND KINASE DOMAINS, RESIDUES 787-939,990-1171
Mutation: YES
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PFASTBAC / Cell line (production host): SF9 / Production host: SPODOPTERA FRUGIPERDA (fall armyworm)
References: UniProt: P35968, receptor protein-tyrosine kinase
#2: Chemical ChemComp-B49 / N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carbo xamide / SUNITINIB


Mass: 398.474 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C22H27FN4O2 / Comment: medication, anticancer, inhibitor*YM
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 87 / Source method: isolated from a natural source / Formula: H2O
Compound detailsENGINEERED RESIDUE IN CHAIN A, GLU 990 TO VAL

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.6 Å3/Da / Density % sol: 53.2 % / Description: NONE
Crystal growTemperature: 286 K / Method: vapor diffusion, hanging drop / pH: 6.2
Details: CRYSTALS WERE GROWN AT 13 DEGREES C BY THE HANGING DROP VAPOR DIFFUSION METHOD USING PRECIPITANT SOLUTIONS CONTAINING: 0.222 M SODIUM CITRATE (PH 6.3) AND 17% (W/V) POLYETHYLENE GLYCOL 3350

-
Data collection

DiffractionMean temperature: 87 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-D / Wavelength: 1
DetectorType: MARRESEARCH / Detector: IMAGE PLATE / Date: Dec 1, 2008
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.8→40 Å / Num. obs: 9095 / % possible obs: 92.4 % / Observed criterion σ(I): 2 / Redundancy: 3.4 % / Biso Wilson estimate: 26.5 Å2 / Rmerge(I) obs: 0.06 / Net I/σ(I): 19.5
Reflection shellResolution: 2.8→2.9 Å / Redundancy: 2.2 % / Rmerge(I) obs: 0.23 / Mean I/σ(I) obs: 2.2 / % possible all: 55.7

-
Processing

Software
NameVersionClassification
CNS2005refinement
HKL-2000data reduction
SCALEPACKdata scaling
CCP4phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 4AGC

4agc


Resolution: 2.81→37.69 Å / Rfactor Rfree error: 0.018 / Data cutoff high absF: 64241.02 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 0
RfactorNum. reflection% reflectionSelection details
Rfree0.307 282 3.2 %RANDOM
Rwork0.21 ---
obs0.21 8793 88.2 %-
Solvent computationSolvent model: FLAT MODEL / Bsol: 54.0271 Å2 / ksol: 0.33577 e/Å3
Displacement parametersBiso mean: 66.3 Å2
Baniso -1Baniso -2Baniso -3
1--11.96 Å20 Å2-8.38 Å2
2---3.31 Å20 Å2
3---15.28 Å2
Refine analyze
FreeObs
Luzzati coordinate error0.49 Å0.34 Å
Luzzati d res low-5 Å
Luzzati sigma a0.39 Å0.4 Å
Refinement stepCycle: LAST / Resolution: 2.81→37.69 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2430 0 29 87 2546
Refine LS restraints
Refine-IDTypeDev idealDev ideal target
X-RAY DIFFRACTIONc_bond_d0.007
X-RAY DIFFRACTIONc_bond_d_na
X-RAY DIFFRACTIONc_bond_d_prot
X-RAY DIFFRACTIONc_angle_d
X-RAY DIFFRACTIONc_angle_d_na
X-RAY DIFFRACTIONc_angle_d_prot
X-RAY DIFFRACTIONc_angle_deg1
X-RAY DIFFRACTIONc_angle_deg_na
X-RAY DIFFRACTIONc_angle_deg_prot
X-RAY DIFFRACTIONc_dihedral_angle_d22.2
X-RAY DIFFRACTIONc_dihedral_angle_d_na
X-RAY DIFFRACTIONc_dihedral_angle_d_prot
X-RAY DIFFRACTIONc_improper_angle_d0.71
X-RAY DIFFRACTIONc_improper_angle_d_na
X-RAY DIFFRACTIONc_improper_angle_d_prot
X-RAY DIFFRACTIONc_mcbond_it1.521.5
X-RAY DIFFRACTIONc_mcangle_it2.722
X-RAY DIFFRACTIONc_scbond_it1.792
X-RAY DIFFRACTIONc_scangle_it2.932.5
Refine LS restraints NCSNCS model details: NONE
LS refinement shellResolution: 2.8→2.98 Å / Rfactor Rfree error: 0.064 / Total num. of bins used: 6
RfactorNum. reflection% reflection
Rfree0.325 26 3.1 %
Rwork0.299 805 -
obs--51 %
Xplor file
Refine-IDSerial noParam fileTopol file
X-RAY DIFFRACTION1PROTEIN_REP.PARAMPROTEIN.TOP
X-RAY DIFFRACTION2DNA-RNA_REP.PARAMDNA-RNA.TOP
X-RAY DIFFRACTION3WATER_REP.PARAMWATER.TOP
X-RAY DIFFRACTION4ION.PARAMION.TOP
X-RAY DIFFRACTION5MOL.PARAMMOL.TOP

+
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