[English] 日本語
Yorodumi
- PDB-2p2i: Crystal structure of the VEGFR2 kinase domain in complex with a n... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2p2i
TitleCrystal structure of the VEGFR2 kinase domain in complex with a nicotinamide inhibitor
ComponentsVascular endothelial growth factor receptor 2
KeywordsTRANSFERASE / receptor tyrosine kinase / KDR
Function / homology
Function and homology information


cellular response to hydrogen sulfide / blood vessel endothelial cell differentiation / regulation of bone development / Signaling by membrane-tethered fusions of PDGFRA or PDGFRB / vascular endothelial growth factor binding / Neurophilin interactions with VEGF and VEGFR / vascular endothelial growth factor receptor-2 signaling pathway / VEGF binds to VEGFR leading to receptor dimerization / endothelium development / endocardium development ...cellular response to hydrogen sulfide / blood vessel endothelial cell differentiation / regulation of bone development / Signaling by membrane-tethered fusions of PDGFRA or PDGFRB / vascular endothelial growth factor binding / Neurophilin interactions with VEGF and VEGFR / vascular endothelial growth factor receptor-2 signaling pathway / VEGF binds to VEGFR leading to receptor dimerization / endothelium development / endocardium development / vascular wound healing / vascular endothelial growth factor receptor activity / regulation of hematopoietic progenitor cell differentiation / post-embryonic camera-type eye morphogenesis / positive regulation of vasculogenesis / endothelial cell differentiation / lymph vessel development / mesenchymal cell proliferation / positive regulation of BMP signaling pathway / surfactant homeostasis / cell migration involved in sprouting angiogenesis / epithelial cell maturation / anchoring junction / positive regulation of positive chemotaxis / embryonic hemopoiesis / vascular endothelial growth factor signaling pathway / positive regulation of mesenchymal cell proliferation / positive regulation of endothelial cell chemotaxis / positive regulation of cell migration involved in sprouting angiogenesis / positive regulation of mitochondrial fission / branching involved in blood vessel morphogenesis / positive regulation of mitochondrial depolarization / lung alveolus development / positive regulation of stem cell proliferation / : / sorting endosome / growth factor binding / positive regulation of focal adhesion assembly / positive regulation of macroautophagy / regulation of MAPK cascade / semaphorin-plexin signaling pathway / positive regulation of blood vessel endothelial cell migration / cellular response to vascular endothelial growth factor stimulus / cell fate commitment / vasculogenesis / Integrin cell surface interactions / vascular endothelial growth factor receptor signaling pathway / negative regulation of endothelial cell apoptotic process / coreceptor activity / peptidyl-tyrosine autophosphorylation / calcium ion homeostasis / ovarian follicle development / cell surface receptor protein tyrosine kinase signaling pathway / positive regulation of endothelial cell proliferation / transmembrane receptor protein tyrosine kinase activity / positive regulation of endothelial cell migration / VEGFR2 mediated cell proliferation / stem cell proliferation / epithelial cell proliferation / Hsp90 protein binding / receptor protein-tyrosine kinase / VEGFA-VEGFR2 Pathway / peptidyl-tyrosine phosphorylation / positive regulation of angiogenesis / integrin binding / cell migration / cell junction / regulation of cell shape / protein tyrosine kinase activity / angiogenesis / negative regulation of neuron apoptotic process / protein autophosphorylation / positive regulation of MAPK cascade / positive regulation of ERK1 and ERK2 cascade / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / early endosome / receptor complex / endosome / positive regulation of cell migration / cadherin binding / positive regulation of protein phosphorylation / membrane raft / external side of plasma membrane / negative regulation of gene expression / positive regulation of cell population proliferation / 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 / 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 ...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 / 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-608 / Vascular endothelial growth factor receptor 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.4 Å
AuthorsWhittington, D.A. / Kim, J.L. / Long, A.M. / Rose, P. / Gu, Y. / Zhao, H.
CitationJournal: J.Med.Chem. / Year: 2007
Title: Evolution of a Highly Selective and Potent 2-(Pyridin-2-yl)-1,3,5-triazine Tie-2 Kinase Inhibitor
Authors: Hodous, B.L. / Geuns-Meyer, S.D. / Hughes, P.E. / Albrecht, B.K. / Bellon, S. / Bready, J. / Caenepeel, S. / Cee, V.J. / Chaffee, S.C. / Coxon, A. / Emery, M. / Fretland, J. / Gallant, P. / ...Authors: Hodous, B.L. / Geuns-Meyer, S.D. / Hughes, P.E. / Albrecht, B.K. / Bellon, S. / Bready, J. / Caenepeel, S. / Cee, V.J. / Chaffee, S.C. / Coxon, A. / Emery, M. / Fretland, J. / Gallant, P. / Gu, Y. / Hoffman, D. / Johnson, R.E. / Kendall, R. / Kim, J.L. / Long, A.M. / Morrison, M. / Olivieri, P.R. / Patel, V.F. / Polverino, A. / Rose, P. / Tempest, P. / Wang, L. / Whittington, D.A. / Zhao, H.
History
DepositionMar 7, 2007Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 20, 2007Provider: repository / Type: Initial release
Revision 1.1May 1, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Version format compliance
Revision 1.3Aug 16, 2017Group: Refinement description / Source and taxonomy / Category: entity_src_gen / software
Revision 1.4Oct 20, 2021Group: Database references / Derived calculations / Category: 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
Revision 1.5Feb 21, 2024Group: Data collection / Category: chem_comp_atom / chem_comp_bond
Revision 1.6Nov 13, 2024Group: Structure summary / Category: pdbx_entry_details

-
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)73,3584
Polymers72,5652
Non-polymers7932
Water2,198122
1
A: Vascular endothelial growth factor receptor 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,6792
Polymers36,2831
Non-polymers3961
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)36,6792
Polymers36,2831
Non-polymers3961
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)55.42, 67.06, 88.51
Angle α, β, γ (deg.)90.00, 94.51, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Vascular endothelial growth factor receptor 2 / VEGFR-2 / Kinase insert domain receptor / Protein-tyrosine kinase receptor Flk-1 / CD309 antigen


Mass: 36282.613 Da / Num. of mol.: 2 / Fragment: kinase domain / Mutation: C817A, E990V, (delete 940-989)
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KDR, FLK1 / Production host: Trichoplusia ni (cabbage looper)
References: UniProt: P35968, receptor protein-tyrosine kinase
#2: Chemical ChemComp-608 / N-(4-phenoxyphenyl)-2-[(pyridin-4-ylmethyl)amino]nicotinamide


Mass: 396.441 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C24H20N4O2
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 122 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.27 Å3/Da / Density % sol: 45.78 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 8
Details: pH 8.0, VAPOR DIFFUSION, HANGING DROP, temperature 277K

-
Data collection

Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.2
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthRelative weight: 1
ReflectionResolution: 2.4→40 Å / Num. obs: 23837 / % possible obs: 94.1 % / Redundancy: 2.5 % / Rmerge(I) obs: 0.098 / Χ2: 1.248 / Net I/σ(I): 9.6
Reflection shellResolution: 2.4→2.49 Å / Rmerge(I) obs: 0.415 / Mean I/σ(I) obs: 2 / Num. unique all: 2186 / Χ2: 1.01 / % possible all: 87.6

-
Phasing

PhasingMethod: molecular replacement
Phasing MRRfactor: 0.565 / Cor.coef. Fo:Fc: 0.219
Highest resolutionLowest resolution
Translation3.5 Å20 Å

-
Processing

Software
NameVersionClassificationNB
SCALEPACKdata scaling
EPMR2.4phasing
CNSrefinement
PDB_EXTRACT1.401data extraction
DENZOdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.4→36.86 Å / Rfactor Rfree error: 0.008 / Data cutoff high absF: 1700177.875 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 0
RfactorNum. reflection% reflectionSelection details
Rfree0.266 1128 4.8 %RANDOM
Rwork0.222 ---
obs-23375 91.8 %-
Solvent computationSolvent model: FLAT MODEL / Bsol: 30.461 Å2 / ksol: 0.349 e/Å3
Displacement parametersBiso mean: 32 Å2
Baniso -1Baniso -2Baniso -3
1--8.69 Å20 Å20.11 Å2
2---3.25 Å20 Å2
3---11.94 Å2
Refine analyze
FreeObs
Luzzati coordinate error0.38 Å0.32 Å
Luzzati d res low-5 Å
Luzzati sigma a0.46 Å0.56 Å
Refinement stepCycle: LAST / Resolution: 2.4→36.86 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4341 0 60 122 4523
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONc_bond_d0.009
X-RAY DIFFRACTIONc_angle_deg1.39
X-RAY DIFFRACTIONc_dihedral_angle_d22.5
X-RAY DIFFRACTIONc_improper_angle_d0.821
LS refinement shellResolution: 2.4→2.55 Å / Rfactor Rfree error: 0.026 / Total num. of bins used: 6
RfactorNum. reflection% reflection
Rfree0.323 149 4.4 %
Rwork0.335 3247 -
obs--81.3 %

+
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