[English] 日本語
Yorodumi
- PDB-2oh4: Crystal structure of Vegfr2 with a benzimidazole-urea inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2oh4
TitleCrystal structure of Vegfr2 with a benzimidazole-urea inhibitor
ComponentsVascular endothelial growth factor receptor 2
KeywordsTRANSFERASE / Vascular endothelial growth factor receptor 2 / Tyrosine-protein kinase / Angiogenesis / ATP-binding / Phosphorylation / Kinase insert domain receptor / Protein-tyrosine kinase receptor Flk-1
Function / homology
Function and homology information


positive regulation of nitric oxide-cGMP mediated signal transduction / 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 ...positive regulation of nitric oxide-cGMP mediated signal transduction / 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 / mesenchymal cell proliferation / positive regulation of vasculogenesis / 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 / positive regulation of endothelial cell chemotaxis / anchoring junction / embryonic hemopoiesis / 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 stem cell proliferation / positive regulation of mitochondrial depolarization / growth factor binding / sorting endosome / regulation of MAPK cascade / semaphorin-plexin signaling pathway / positive regulation of macroautophagy / cellular response to vascular endothelial growth factor stimulus / positive regulation of focal adhesion assembly / cell fate commitment / positive regulation of blood vessel endothelial cell migration / Integrin cell surface interactions / vascular endothelial growth factor receptor signaling pathway / negative regulation of endothelial cell apoptotic process / vasculogenesis / peptidyl-tyrosine autophosphorylation / calcium ion homeostasis / coreceptor activity / ovarian follicle development / 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 / 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 / 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 / peptidyl-tyrosine phosphorylation / VEGFA-VEGFR2 Pathway / positive regulation of angiogenesis / integrin binding / cell junction / cell migration / regulation of cell shape / positive regulation of protein phosphorylation / protein autophosphorylation / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / protein tyrosine kinase activity / angiogenesis / negative regulation of neuron apoptotic process / early endosome / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor complex / positive regulation of ERK1 and ERK2 cascade / positive regulation of MAPK cascade / endosome / positive regulation of cell migration / cadherin binding / membrane raft / external side of plasma membrane / negative regulation of gene expression
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. / Tyrosine-protein kinase, active site / Immunoglobulin subtype / Immunoglobulin / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Phosphorylase Kinase; domain 1 / Ig-like domain profile. / Immunoglobulin-like domain / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Immunoglobulin-like domain superfamily / 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-GIG / Vascular endothelial growth factor receptor 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.05 Å
AuthorsNolte, R.T. / Wang, L.
CitationJournal: J.Med.Chem. / Year: 2007
Title: Discovery of Novel Benzimidazoles as Potent Inhibitors of TIE-2 and VEGFR-2 Tyrosine Kinase Receptors.
Authors: Hasegawa, M. / Nishigaki, N. / Washio, Y. / Kano, K. / Harris, P.A. / Sato, H. / Mori, I. / West, R.I. / Shibahara, M. / Toyoda, H. / Wang, L. / Nolte, R.T. / Veal, J.M. / Cheung, M.
History
DepositionJan 9, 2007Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 18, 2007Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Advisory / Version format compliance
Revision 1.2Jun 14, 2017Group: Advisory / Database references ...Advisory / Database references / Source and taxonomy / Structure summary
Category: entity_name_com / entity_src_gen ...entity_name_com / entity_src_gen / pdbx_unobs_or_zero_occ_residues / struct_keywords / struct_ref_seq / struct_ref_seq_dif
Item: _entity_name_com.name / _pdbx_unobs_or_zero_occ_residues.auth_seq_id ..._entity_name_com.name / _pdbx_unobs_or_zero_occ_residues.auth_seq_id / _struct_keywords.text / _struct_ref_seq.pdbx_auth_seq_align_beg / _struct_ref_seq.pdbx_auth_seq_align_end / _struct_ref_seq.seq_align_beg
Revision 1.3Oct 18, 2017Group: Refinement description / Category: software
Item: _software.classification / _software.contact_author ..._software.classification / _software.contact_author / _software.contact_author_email / _software.date / _software.language / _software.location / _software.name / _software.type / _software.version
Revision 1.4Aug 30, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_conn / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_conn.pdbx_leaving_atom_flag / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.5Nov 15, 2023Group: Data collection / Category: chem_comp_atom / chem_comp_bond / Item: _chem_comp_atom.atom_id / _chem_comp_bond.atom_id_2
Revision 1.6Oct 16, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

-
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)37,1044
Polymers36,4091
Non-polymers6963
Water3,747208
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)38.370, 94.250, 95.754
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
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: 36408.680 Da / Num. of mol.: 1 / Fragment: kinase domain / Mutation: E990V, Deletion of residues 940-989
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KDR, FLK1, VEGFR2 / Production host: Escherichia coli (E. coli)
References: UniProt: P35968, receptor protein-tyrosine kinase
#2: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4
#3: Chemical ChemComp-GIG / METHYL (5-{4-[({[2-FLUORO-5-(TRIFLUOROMETHYL)PHENYL]AMINO}CARBONYL)AMINO]PHENOXY}-1H-BENZIMIDAZOL-2-YL)CARBAMATE


Mass: 503.406 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H17F4N5O4
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 208 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.5 Å3/Da / Density % sol: 51.1 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7.2
Details: pH 7.2, VAPOR DIFFUSION, HANGING DROP, temperature 277K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: MAR CCD 165 mm / Detector: CCD / Date: Feb 1, 2001
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.05→47.67 Å / Num. obs: 22437 / % possible obs: 99.49 % / Redundancy: 6.7 % / Rmerge(I) obs: 0.064 / Χ2: 1.645 / Net I/σ(I): 24.6
Reflection shellResolution: 2.05→2.12 Å / Rmerge(I) obs: 0.179 / Mean I/σ(I) obs: 2.029 / Num. unique all: 2089 / Χ2: 0.957 / % possible all: 93.6

-
Processing

Software
NameVersionClassificationNB
DENZOdata reduction
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACT2data extraction
MAR345data collection
HKL-2000data reduction
AMoREphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1YWN

1ywn


Resolution: 2.05→47.67 Å / Cor.coef. Fo:Fc: 0.954 / Cor.coef. Fo:Fc free: 0.934 / SU B: 7.332 / SU ML: 0.108 / TLS residual ADP flag: LIKELY RESIDUAL / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.191 / ESU R Free: 0.168 / Stereochemistry target values: MAXIMUM LIKELIHOOD
RfactorNum. reflection% reflectionSelection details
Rfree0.231 726 3.2 %RANDOM
Rwork0.187 ---
obs0.189 22437 99.49 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 44.66 Å2
Baniso -1Baniso -2Baniso -3
1--0.17 Å20 Å20 Å2
2--1.58 Å20 Å2
3----1.42 Å2
Refinement stepCycle: LAST / Resolution: 2.05→47.67 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2378 0 46 208 2632
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.010.0222515
X-RAY DIFFRACTIONr_bond_other_d0.0010.021716
X-RAY DIFFRACTIONr_angle_refined_deg1.1631.993416
X-RAY DIFFRACTIONr_angle_other_deg0.87834161
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.7055305
X-RAY DIFFRACTIONr_dihedral_angle_2_deg33.39223.182110
X-RAY DIFFRACTIONr_dihedral_angle_3_deg12.01915422
X-RAY DIFFRACTIONr_dihedral_angle_4_deg19.7761518
X-RAY DIFFRACTIONr_chiral_restr0.0750.2362
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.022770
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02522
X-RAY DIFFRACTIONr_nbd_refined0.2180.2502
X-RAY DIFFRACTIONr_nbd_other0.190.21813
X-RAY DIFFRACTIONr_nbtor_refined0.1810.21237
X-RAY DIFFRACTIONr_nbtor_other0.0830.21216
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1590.2156
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.0920.28
X-RAY DIFFRACTIONr_symmetry_vdw_other0.1890.225
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.1220.213
X-RAY DIFFRACTIONr_mcbond_it0.721.51577
X-RAY DIFFRACTIONr_mcbond_other0.1441.5610
X-RAY DIFFRACTIONr_mcangle_it1.14122435
X-RAY DIFFRACTIONr_scbond_it1.50931113
X-RAY DIFFRACTIONr_scangle_it2.334.5981
LS refinement shellResolution: 2.05→2.103 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.206 48 -
Rwork0.186 1525 -
obs-1573 95.62 %
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)
12.03180.38440.18844.04010.21994.35640.06480.08810.0374-0.0414-0.03570.26270.1103-0.1636-0.0291-0.1823-0.01620.0008-0.2247-0.0125-0.22662.11834.2236.18
22.13940.33710.57652.60081.12655.2449-0.0314-0.2041-0.02260.0828-0.1230.1690.1537-0.61610.1544-0.2583-0.02410.003-0.1306-0.0344-0.26057.68441.43132.389
Refinement TLS group

Refine-ID: X-RAY DIFFRACTION / Selection: ALL / Auth asym-ID: A / Label asym-ID: A

IDRefine TLS-IDAuth seq-IDLabel seq-ID
11817 - 92015 - 118
22921 - 1166119 - 313

+
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