[English] 日本語
Yorodumi
- PDB-8yki: FGFR-1 in complex with ligand tasurgratinib -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8yki
TitleFGFR-1 in complex with ligand tasurgratinib
ComponentsFibroblast growth factor receptor 1
KeywordsTRANSFERASE / FGF RECEPTOR KINASE / PROTEROS BIOSTRUCTURES GMBH
Function / homology
Function and homology information


Signaling by FGFR1 amplification mutants / negative regulation of fibroblast growth factor production / positive regulation of mitotic cell cycle DNA replication / regulation of extrinsic apoptotic signaling pathway in absence of ligand / Signaling by plasma membrane FGFR1 fusions / diphosphate metabolic process / regulation of phosphate transport / regulation of lateral mesodermal cell fate specification / FGFR1c and Klotho ligand binding and activation / vitamin D3 metabolic process ...Signaling by FGFR1 amplification mutants / negative regulation of fibroblast growth factor production / positive regulation of mitotic cell cycle DNA replication / regulation of extrinsic apoptotic signaling pathway in absence of ligand / Signaling by plasma membrane FGFR1 fusions / diphosphate metabolic process / regulation of phosphate transport / regulation of lateral mesodermal cell fate specification / FGFR1c and Klotho ligand binding and activation / vitamin D3 metabolic process / cementum mineralization / positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway / regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling / receptor-receptor interaction / response to sodium phosphate / fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development / ventricular zone neuroblast division / Epithelial-Mesenchymal Transition (EMT) during gastrulation / auditory receptor cell development / positive regulation of phospholipase activity / chordate embryonic development / positive regulation of parathyroid hormone secretion / mesenchymal cell proliferation / paraxial mesoderm development / regulation of postsynaptic density assembly / FGFR1b ligand binding and activation / Signaling by activated point mutants of FGFR1 / FGFR1c ligand binding and activation / organ induction / Downstream signaling of activated FGFR1 / branching involved in salivary gland morphogenesis / Phospholipase C-mediated cascade: FGFR1 / lung-associated mesenchyme development / cell projection assembly / outer ear morphogenesis / embryonic limb morphogenesis / positive regulation of endothelial cell chemotaxis / positive regulation of vascular endothelial cell proliferation / positive regulation of mesenchymal cell proliferation / ureteric bud development / skeletal system morphogenesis / cardiac muscle cell proliferation / middle ear morphogenesis / inner ear morphogenesis / phosphatidylinositol-mediated signaling / PI-3K cascade:FGFR1 / Formation of paraxial mesoderm / positive regulation of stem cell proliferation / midbrain development / fibroblast growth factor binding / regulation of cell differentiation / PI3K Cascade / epithelial to mesenchymal transition / fibroblast growth factor receptor signaling pathway / positive regulation of blood vessel endothelial cell migration / chondrocyte differentiation / positive regulation of MAP kinase activity / fibroblast growth factor receptor activity / calcium ion homeostasis / cell maturation / SHC-mediated cascade:FGFR1 / positive regulation of cardiac muscle cell proliferation / cellular response to fibroblast growth factor stimulus / FRS-mediated FGFR1 signaling / Signaling by FGFR1 in disease / positive regulation of neuron differentiation / NCAM signaling for neurite out-growth / SH2 domain binding / Signal transduction by L1 / stem cell proliferation / skeletal system development / positive regulation of cell differentiation / stem cell differentiation / Negative regulation of FGFR1 signaling / sensory perception of sound / peptidyl-tyrosine phosphorylation / receptor protein-tyrosine kinase / positive regulation of neuron projection development / neuron migration / neuron projection development / Constitutive Signaling by Aberrant PI3K in Cancer / MAPK cascade / cell migration / PIP3 activates AKT signaling / heparin binding / protein autophosphorylation / RAF/MAP kinase cascade / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / cytoplasmic vesicle / protein tyrosine kinase activity / angiogenesis / in utero embryonic development / gene expression / receptor complex / postsynapse / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of MAPK cascade / protein phosphorylation / positive regulation of cell population proliferation / glutamatergic synapse
Similarity search - Function
Fibroblast growth factor receptor 1, catalytic domain / Fibroblast growth factor receptor family / Immunoglobulin / Immunoglobulin domain / Immunoglobulin I-set / Immunoglobulin I-set domain / : / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Tyrosine-protein kinase, catalytic domain ...Fibroblast growth factor receptor 1, catalytic domain / Fibroblast growth factor receptor family / 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 / 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
Similarity search - Domain/homology
: / Fibroblast growth factor receptor 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.79 Å
AuthorsIkemori-Kawada, M. / Watanabe Miyano, S.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Anticancer Res. / Year: 2024
Title: Antitumor Activity of Tasurgratinib as an Orally Available FGFR1-3 Inhibitor in Cholangiocarcinoma Models With FGFR2-fusion.
Authors: Kawano, S. / Kawada, M.I. / Fukushima, S. / Arai, Y. / Shibata, T. / Miyano, S.W.
History
DepositionMar 5, 2024Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jun 12, 2024Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Fibroblast growth factor receptor 1
B: Fibroblast growth factor receptor 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)73,4796
Polymers72,2332
Non-polymers1,2464
Water18010
1
A: Fibroblast growth factor receptor 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,7403
Polymers36,1161
Non-polymers6232
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area990 Å2
ΔGint-1 kcal/mol
Surface area14470 Å2
MethodPISA
2
B: Fibroblast growth factor receptor 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,7403
Polymers36,1161
Non-polymers6232
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1030 Å2
ΔGint-2 kcal/mol
Surface area14100 Å2
MethodPISA
Unit cell
Length a, b, c (Å)214.362, 50.260, 64.906
Angle α, β, γ (deg.)90.000, 107.000, 90.000
Int Tables number5
Space group name H-MC121
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21B

NCS domain segments:

Component-ID: _ / Ens-ID: 1 / Beg auth comp-ID: GLU / Beg label comp-ID: GLU / End auth comp-ID: THR / End label comp-ID: THR / Refine code: _ / Auth seq-ID: 464 - 761 / Label seq-ID: 7 - 304

Dom-IDAuth asym-IDLabel asym-ID
1AA
2BB

-
Components

#1: Protein Fibroblast growth factor receptor 1 / FGFR-1 / Basic fibroblast growth factor receptor 1 / BFGFR / bFGF-R-1 / Fms-like tyrosine kinase 2 ...FGFR-1 / Basic fibroblast growth factor receptor 1 / BFGFR / bFGF-R-1 / Fms-like tyrosine kinase 2 / FLT-2 / N-sam / Proto-oncogene c-Fgr


Mass: 36116.473 Da / Num. of mol.: 2 / Mutation: C488A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: FGFR1, BFGFR, CEK, FGFBR, FLG, FLT2, HBGFR / Cell line (production host): Sf9 / Production host: Spodoptera (butterflies/moths)
References: UniProt: P11362, receptor protein-tyrosine kinase
#2: Chemical ChemComp-A1LY1 / Tasurgratinib / E-7090


Mass: 587.666 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C32H37N5O6 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Cl
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 10 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.31 Å3/Da / Density % sol: 46.86 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / Details: 18% w/v PEG 3350, 0.2M (NH4)2 TARTRATE

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 0.99977 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Feb 7, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.99977 Å / Relative weight: 1
ReflectionResolution: 2.79→102.5 Å / Num. obs: 16388 / % possible obs: 97.5 % / Redundancy: 2.8 % / Rmerge(I) obs: 0.046 / Net I/σ(I): 19.3
Reflection shellResolution: 2.79→3.04 Å / Redundancy: 2.9 % / Rmerge(I) obs: 0.446 / Num. unique obs: 3721 / % possible all: 98.9

-
Processing

Software
NameVersionClassification
REFMAC5.8.0155refinement
XDSdata reduction
XSCALEdata scaling
REFMACphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: NONE

Resolution: 2.79→102.5 Å / Cor.coef. Fo:Fc: 0.931 / Cor.coef. Fo:Fc free: 0.901 / SU B: 42.058 / SU ML: 0.38 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.417 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: U VALUES : WITH TLS ADDED HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.2879 680 4.1 %RANDOM
Rwork0.2403 ---
obs0.2421 15708 97.62 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 173.02 Å2 / Biso mean: 88.27 Å2 / Biso min: 31.65 Å2
Baniso -1Baniso -2Baniso -3
1--0.66 Å2-0 Å2-2.23 Å2
2--5.14 Å20 Å2
3----2.62 Å2
Refinement stepCycle: final / Resolution: 2.79→102.5 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4232 0 82 10 4324
Biso mean--83.57 57.8 -
Num. residues----533
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0110.0194129
X-RAY DIFFRACTIONr_bond_other_d0.0020.023938
X-RAY DIFFRACTIONr_angle_refined_deg1.3661.9985607
X-RAY DIFFRACTIONr_angle_other_deg1.14638983
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.9165525
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.35223.673147
X-RAY DIFFRACTIONr_dihedral_angle_3_deg11.73115.111674
X-RAY DIFFRACTIONr_dihedral_angle_4_deg10.8281522
X-RAY DIFFRACTIONr_chiral_restr0.070.2637
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.0214607
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02867
X-RAY DIFFRACTIONr_mcbond_it2.3725.372124
X-RAY DIFFRACTIONr_mcbond_other2.3725.3692123
X-RAY DIFFRACTIONr_mcangle_it3.8579.0422641
Refine LS restraints NCS

Ens-ID: 1 / Number: 14710 / Refine-ID: X-RAY DIFFRACTION / Type: interatomic distance / Rms dev position: 0.05 Å / Weight position: 0.05

Dom-IDAuth asym-ID
1A
2B
LS refinement shellResolution: 2.79→2.862 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.384 51 -
Rwork0.324 1131 -
all-1182 -
obs--98.99 %
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)
15.3683-0.54511.20893.9931-2.6236.88680.0637-0.1362-0.33260.0009-0.0318-0.06380.7930.1405-0.0320.12310.0318-0.00880.5286-0.00640.1705-6.609-43.17715.661
23.97370.1447-0.13060.5985-0.23917.1226-0.1054-0.1354-0.09330.00690.10620.4040.0307-0.5287-0.00090.00460.02790.00790.50550.050.3084-23.485-34.114-3.76
35.3379-2.16770.13686.3406-1.64276.560.0656-0.02110.42520.02050.1137-0.1412-0.3509-0.0763-0.17930.11760.0108-0.01860.56830.03740.2524-36.606-18.10736.797
48.6240.54461.56833.0004-0.0185.1486-0.12991.11390.2783-0.4838-0.13520.2596-0.40020.00210.2650.28620.13720.01680.97390.15850.4722-51.765-11.44614.924
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A464 - 563
2X-RAY DIFFRACTION2A564 - 762
3X-RAY DIFFRACTION3B459 - 563
4X-RAY DIFFRACTION4B564 - 761

+
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