[English] 日本語
Yorodumi
- PDB-3vo3: Crystal Structure of the Kinase domain of Human VEGFR2 with imida... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3vo3
TitleCrystal Structure of the Kinase domain of Human VEGFR2 with imidazo[1,2-b]pyridazine derivative
ComponentsVascular endothelial growth factor receptor 2VEGF receptor
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / vegfr2 / kinase domain / Tyrosin-protein kinase / TRANSFERASE-TRANSFERASE INHIBITOR complex
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 / vascular endothelial growth factor binding / Neurophilin interactions with VEGF and VEGFR / endothelium development / vascular endothelial growth factor receptor-2 signaling pathway / 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 / vascular endothelial growth factor binding / Neurophilin interactions with VEGF and VEGFR / endothelium development / vascular endothelial growth factor receptor-2 signaling pathway / VEGF binds to VEGFR leading to receptor dimerization / endocardium development / vascular wound healing / vascular endothelial growth factor receptor activity / regulation of hematopoietic progenitor cell differentiation / post-embryonic camera-type eye morphogenesis / endothelial cell differentiation / mesenchymal cell proliferation / positive regulation of vasculogenesis / lymph vessel development / positive regulation of BMP signaling pathway / surfactant homeostasis / cell migration involved in sprouting angiogenesis / anchoring junction / epithelial cell maturation / positive regulation of positive chemotaxis / embryonic hemopoiesis / vascular endothelial growth factor signaling pathway / positive regulation of endothelial cell chemotaxis / positive regulation of mesenchymal cell proliferation / positive regulation of mitochondrial depolarization / branching involved in blood vessel morphogenesis / positive regulation of cell migration involved in sprouting angiogenesis / positive regulation of mitochondrial fission / lung alveolus development / positive regulation of stem cell proliferation / positive regulation of nitric-oxide synthase biosynthetic process / sorting endosome / growth factor binding / positive regulation of focal adhesion assembly / regulation of MAPK cascade / semaphorin-plexin signaling pathway / positive regulation of macroautophagy / : / positive regulation of blood vessel endothelial cell migration / cellular response to vascular endothelial growth factor stimulus / cell fate commitment / calcium ion homeostasis / Integrin cell surface interactions / vasculogenesis / vascular endothelial growth factor receptor signaling pathway / coreceptor activity / negative regulation of endothelial cell apoptotic process / peptidyl-tyrosine autophosphorylation / ovarian follicle development / positive regulation of endothelial cell proliferation / transmembrane receptor protein tyrosine kinase activity / positive regulation of endothelial cell migration / VEGFR2 mediated cell proliferation / epithelial cell proliferation / stem cell proliferation / cell surface receptor protein tyrosine kinase signaling pathway / Hsp90 protein binding / receptor protein-tyrosine kinase / VEGFA-VEGFR2 Pathway / peptidyl-tyrosine phosphorylation / positive regulation of angiogenesis / cell migration / integrin binding / cell junction / regulation of cell shape / protein tyrosine kinase activity / angiogenesis / negative regulation of neuron apoptotic process / positive regulation of MAPK cascade / protein autophosphorylation / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / early endosome / positive regulation of ERK1 and ERK2 cascade / receptor complex / endosome / positive regulation of cell migration / cadherin binding / membrane raft / positive regulation of protein phosphorylation / external side of plasma membrane / negative regulation of gene expression / positive regulation of cell population proliferation / negative regulation of apoptotic process / Golgi apparatus / endoplasmic reticulum / 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 / Tyrosine-protein kinase, receptor class III, conserved site / Receptor tyrosine kinase class III signature. / Immunoglobulin domain / Immunoglobulin / Immunoglobulin domain / Immunoglobulin I-set ...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 / 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 / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; 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-0KF / Vascular endothelial growth factor receptor 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.52 Å
AuthorsOki, H. / Okada, K.
CitationJournal: Bioorg.Med.Chem. / Year: 2013
Title: Discovery of N-[5-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)-2-methylphenyl]-1,3-dimethyl-1H-pyrazole-5-carboxamide (TAK-593), a highly potent VEGFR2 kinase inhibitor
Authors: Miyamoto, N. / Sakai, N. / Hirayama, T. / Miwa, K. / Oguro, Y. / Oki, H. / Okada, K. / Takagi, T. / Iwata, H. / Awazu, Y. / Yamasaki, S. / Takeuchi, T. / Miki, H. / Hori, A. / Imamura, S.
History
DepositionJan 19, 2012Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Mar 6, 2013Provider: repository / Type: Initial release
Revision 1.1Aug 7, 2013Group: Database references
Revision 1.2Mar 20, 2024Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _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)36,8463
Polymers36,3531
Non-polymers4942
Water6,630368
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)134.093, 55.770, 51.572
Angle α, β, γ (deg.)90.000, 94.410, 90.000
Int Tables number5
Space group name H-MC121

-
Components

#1: Protein Vascular endothelial growth factor receptor 2 / VEGF receptor / 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: 36352.875 Da / Num. of mol.: 1 / Fragment: UNP residues 806-1171 / Mutation: truncated residues 940-989
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KDR, FLK1, VEGFR2 / Plasmid: pFastBac / Cell line (production host): Sf9 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P35968, receptor protein-tyrosine kinase
#2: Chemical ChemComp-0KF / N-[3-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)phenyl]-1,3-dimethyl-1H-pyrazole-5-carboxamide


Mass: 431.447 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C22H21N7O3
#3: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL / Ethylene glycol


Mass: 62.068 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6O2
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 368 / 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: 2.64 Å3/Da / Density % sol: 53.49 % / Mosaicity: 0.667 °
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 8.5
Details: 0.1M trisHCl pH 8.5, 1.2M tri-sodium citrate, vapor diffusion, sitting drop, temperature 293K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.3 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 210r / Detector: CCD / Date: Jun 23, 2006
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.52→50 Å / Num. obs: 56337 / % possible obs: 96.3 % / Redundancy: 3.8 % / Biso Wilson estimate: 19.987 Å2 / Rmerge(I) obs: 0.042 / Χ2: 1.01 / Net I/σ(I): 17.9
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allΧ2Diffraction-ID% possible all
1.52-1.572.30.43444681.081176.9
1.57-1.642.70.31852420.997190.2
1.64-1.713.60.25157471.07198.7
1.71-1.84.10.17258270.9981100
1.8-1.924.10.12358581.006199.9
1.92-2.064.10.07458351.0181100
2.06-2.274.10.05458120.889199.9
2.27-2.64.20.04358661.043199.9
2.6-3.274.10.03358600.976199.8
3.27-503.90.02958221.078197.2

-
Processing

Software
NameVersionClassificationNB
SCALEPACKdata scaling
REFMACrefmac_5.2.0019refinement
PDB_EXTRACT3.1data extraction
HKL-2000data collection
HKL-2000data reduction
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.52→39.32 Å / Cor.coef. Fo:Fc: 0.969 / Cor.coef. Fo:Fc free: 0.962 / WRfactor Rfree: 0.196 / WRfactor Rwork: 0.173 / Occupancy max: 1 / Occupancy min: 0.5 / SU B: 2.151 / SU ML: 0.039 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.079 / ESU R Free: 0.066 / Stereochemistry target values: MAXIMUM LIKELIHOOD
RfactorNum. reflection% reflectionSelection details
Rfree0.1821 2867 5.1 %RANDOM
Rwork0.1609 ---
obs0.1619 56331 96.26 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso max: 65.86 Å2 / Biso mean: 23.4135 Å2 / Biso min: 12.66 Å2
Baniso -1Baniso -2Baniso -3
1-0.77 Å20 Å2-0.65 Å2
2---0.98 Å20 Å2
3---0.11 Å2
Refinement stepCycle: LAST / Resolution: 1.52→39.32 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2438 0 36 368 2842
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0080.0222572
X-RAY DIFFRACTIONr_angle_refined_deg1.3331.9823483
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.425313
X-RAY DIFFRACTIONr_dihedral_angle_2_deg32.02622.895114
X-RAY DIFFRACTIONr_dihedral_angle_3_deg12.22315451
X-RAY DIFFRACTIONr_dihedral_angle_4_deg23.1531520
X-RAY DIFFRACTIONr_chiral_restr0.0770.2370
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.021992
X-RAY DIFFRACTIONr_nbd_refined0.1940.21319
X-RAY DIFFRACTIONr_nbtor_refined0.3150.21788
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1370.2354
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.1920.235
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.1010.233
X-RAY DIFFRACTIONr_mcbond_it1.0931.51569
X-RAY DIFFRACTIONr_mcangle_it1.68822482
X-RAY DIFFRACTIONr_scbond_it2.6131128
X-RAY DIFFRACTIONr_scangle_it3.6964.5995
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 20

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
1.52-1.5590.2941590.2193054430474.651
1.559-1.6020.2221650.2013434418386.039
1.602-1.6480.2241900.1763628409793.19
1.648-1.6990.1942120.1653697394299.163
1.699-1.7550.1791920.15736563848100
1.755-1.8160.2031840.15235283712100
1.816-1.8850.1771960.1533395359299.972
1.885-1.9620.1811720.1553294347099.885
1.962-2.0490.1681860.1463146333399.97
2.049-2.1490.1821790.1562978315899.968
2.149-2.2650.1831670.1552846302299.702
2.265-2.4020.1831370.1532717285699.93
2.402-2.5680.1891310.1632553268899.851
2.568-2.7730.1641210.1662394252099.802
2.773-3.0370.181110.172215232899.914
3.037-3.3950.161020.1521966207899.519
3.395-3.9180.1611030.1441724186498.015
3.918-4.7950.178720.1481464158097.215
4.795-6.7640.195570.1941166123299.269
6.764-66.8150.239310.19960971589.51
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
10.1316-0.0209-0.00170.1532-0.03870.1074-0.0014-0.0096-0.00150.01210.0003-0.00010.00250.0010.0012-0.0279-0.00020.00830.0098-0.00060.005333.369-29.517-8.962
20.243-0.00950.02060.1361-0.00580.13780.00260.0075-0.0101-0.0075-0.00130.00950.0075-0.0084-0.0013-0.0288-0.0010.00840.00730.00040.004718.05-28.064-28.994
30.4654-0.5449-0.55480.66720.56950.88080.01660.0587-0.0126-0.024-0.02430.0084-0.0038-0.04910.0077-0.0233-0.00030.00590.01120.00180.007325.615-27.711-13.528
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A812 - 920
2X-RAY DIFFRACTION2A921 - 1168
3X-RAY DIFFRACTION3A2001

+
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