[English] 日本語
Yorodumi
- PDB-3wzd: KDR in complex with ligand lenvatinib -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3wzd
TitleKDR in complex with ligand lenvatinib
ComponentsVascular endothelial growth factor receptor 2
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / KDR RECEPTOR KINASE / TRANSFERASE-TRANSFERASE INHIBITOR complex
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 / 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 / anchoring junction / positive regulation of cell migration involved in sprouting angiogenesis / embryonic hemopoiesis / vascular endothelial growth factor signaling pathway / positive regulation of mesenchymal cell proliferation / lung alveolus development / positive regulation of mitochondrial fission / branching involved in blood vessel morphogenesis / growth factor binding / positive regulation of mitochondrial depolarization / positive regulation of stem cell proliferation / sorting endosome / semaphorin-plexin signaling pathway / regulation of MAPK cascade / positive regulation of macroautophagy / cellular response to vascular endothelial growth factor stimulus / cell fate commitment / positive regulation of focal adhesion assembly / vascular endothelial growth factor receptor activity / 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 / 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 / peptidyl-tyrosine phosphorylation / receptor protein-tyrosine kinase / VEGFA-VEGFR2 Pathway / positive regulation of angiogenesis / integrin binding / cell junction / positive regulation of protein phosphorylation / cell migration / regulation of cell shape / 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 ERK1 and ERK2 cascade / receptor complex / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / endosome / positive regulation of MAPK cascade / positive regulation of cell migration / cadherin binding / membrane raft / external side of plasma membrane / negative regulation of gene expression / 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 / Ig-like domain profile. / Immunoglobulin-like domain / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / 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
2,3-DIHYDROXY-1,4-DITHIOBUTANE / Chem-LEV / Vascular endothelial growth factor receptor 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 1.57 Å
AuthorsOkamoto, K. / Ikemori_Kawada, M. / Inoue, A. / Matsui, J.
CitationJournal: ACS MED.CHEM.LETT. / Year: 2015
Title: Distinct binding mode of multikinase inhibitor lenvatinib revealed by biochemical characterization.
Authors: Okamoto, K. / Ikemori-Kawada, M. / Jestel, A. / von Konig, K. / Funahashi, Y. / Matsushima, T. / Tsuruoka, A. / Inoue, A. / Matsui, J.
History
DepositionSep 24, 2014Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0May 27, 2015Provider: repository / Type: Initial release
Revision 1.1Nov 20, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_entry_details / pdbx_modification_feature / struct_conn / 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_conn.pdbx_leaving_atom_flag / _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)36,82112
Polymers35,3411
Non-polymers1,48011
Water3,837213
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)42.334, 84.225, 46.892
Angle α, β, γ (deg.)90.00, 100.20, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

-
Protein , 1 types, 1 molecules A

#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: 35340.793 Da / Num. of mol.: 1 / Fragment: kinase domain (UNP RESIDUES 814-940, 991-1172) / Mutation: T940V
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KDR, FLK1, VEGFR2 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P35968, receptor protein-tyrosine kinase

-
Non-polymers , 6 types, 224 molecules

#2: Chemical ChemComp-LEV / 4-{3-chloro-4-[(cyclopropylcarbamoyl)amino]phenoxy}-7-methoxyquinoline-6-carboxamide / lenvatinib


Mass: 426.853 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C21H19ClN4O4 / Comment: medication, anticancer*YM
#3: Chemical
ChemComp-DTT / 2,3-DIHYDROXY-1,4-DITHIOBUTANE / 1,4-DITHIOTHREITOL


Mass: 154.251 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C4H10O2S2
#4: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C2H6O2
#5: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#6: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 213 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.45 Å3/Da / Density % sol: 49.91 %
Crystal growTemperature: 277 K / Method: vapor diffusion / pH: 9.5
Details: 0.1M CHES,5-20% PEG 8000, pH 9.5, VAPOR DIFFUSION, temperature 277K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1.00003 Å
DetectorType: PSI PILATUS 6M / Detector: PIXEL
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.00003 Å / Relative weight: 1
ReflectionResolution: 1.57→46.15 Å / Num. obs: 44907 / % possible obs: 99.5 % / Observed criterion σ(I): 0 / Redundancy: 4.2 % / Rmerge(I) obs: 0.06
Reflection shellResolution: 1.57→1.82 Å / Redundancy: 4.2 % / Rmerge(I) obs: 0.444 / % possible all: 99.7

-
Processing

Software
NameVersionClassification
REFMAC5.5.0109refinement
XDSdata reduction
XSCALEdata scaling
RefinementResolution: 1.57→46.15 Å / Cor.coef. Fo:Fc: 0.967 / Cor.coef. Fo:Fc free: 0.956 / SU B: 4.054 / SU ML: 0.07 / Cross valid method: THROUGHOUT / ESU R: 0.084 / ESU R Free: 0.085 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.21188 4082 9.1 %RANDOM
Rwork0.18089 ---
obs0.18372 40823 99.52 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 29.321 Å2
Baniso -1Baniso -2Baniso -3
1-0.11 Å2-0 Å2-1.17 Å2
2---0.51 Å20 Å2
3---0.77 Å2
Refinement stepCycle: LAST / Resolution: 1.57→46.15 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2224 0 89 213 2526
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0120.0192348
X-RAY DIFFRACTIONr_bond_other_d0.0050.022253
X-RAY DIFFRACTIONr_angle_refined_deg1.581.9913166
X-RAY DIFFRACTIONr_angle_other_deg1.0273.0025166
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.9425283
X-RAY DIFFRACTIONr_dihedral_angle_2_deg32.61722.87294
X-RAY DIFFRACTIONr_dihedral_angle_3_deg11.54715387
X-RAY DIFFRACTIONr_dihedral_angle_4_deg19.7191515
X-RAY DIFFRACTIONr_chiral_restr0.0920.2348
X-RAY DIFFRACTIONr_gen_planes_refined0.0090.0212579
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02535
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it2.5842.0431129
X-RAY DIFFRACTIONr_mcbond_other2.5832.0411128
X-RAY DIFFRACTIONr_mcangle_it3.313.4231413
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it4.2042.5071219
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 1.57→1.611 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.319 323 -
Rwork0.296 2945 -
obs--99.66 %
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)
12.43111.17230.64362.9254-0.46282.9128-0.04650.2-0.0791-0.10450.07390.01970.04280.0147-0.02750.06540.01250.00280.0611-0.02060.0483-1.531-13.6488.285
21.1734-0.33960.25182.2429-0.2822.06310.02880.0514-0.00450.04280.0081-0.1104-0.10190.1211-0.03680.0129-0.01170.01030.0415-0.00270.037913.535.83621.758
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A820 - 918
2X-RAY DIFFRACTION2A921 - 1167

+
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