[English] 日本語
Yorodumi
- PDB-6v9c: Crystal structure of FGFR4 kinase domain in complex with covalent... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6v9c
TitleCrystal structure of FGFR4 kinase domain in complex with covalent inhibitor
ComponentsFibroblast growth factor receptor 4
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / tyrosine Kinase inhibitor / covalent inhibitor / FGFR / kinase / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


FGFR4 mutant receptor activation / betaKlotho-mediated ligand binding / regulation of extracellular matrix disassembly / phosphate ion homeostasis / regulation of bile acid biosynthetic process / FGFR4 ligand binding and activation / fibroblast growth factor receptor activity / Phospholipase C-mediated cascade; FGFR4 / positive regulation of DNA biosynthetic process / positive regulation of catalytic activity ...FGFR4 mutant receptor activation / betaKlotho-mediated ligand binding / regulation of extracellular matrix disassembly / phosphate ion homeostasis / regulation of bile acid biosynthetic process / FGFR4 ligand binding and activation / fibroblast growth factor receptor activity / Phospholipase C-mediated cascade; FGFR4 / positive regulation of DNA biosynthetic process / positive regulation of catalytic activity / fibroblast growth factor binding / PI-3K cascade:FGFR4 / positive regulation of proteolysis / regulation of lipid metabolic process / PI3K Cascade / fibroblast growth factor receptor signaling pathway / SHC-mediated cascade:FGFR4 / Signaling by FGFR4 in disease / transport vesicle / FRS-mediated FGFR4 signaling / cholesterol homeostasis / Negative regulation of FGFR4 signaling / receptor protein-tyrosine kinase / peptidyl-tyrosine phosphorylation / Constitutive Signaling by Aberrant PI3K in Cancer / cell migration / PIP3 activates AKT signaling / glucose homeostasis / heparin binding / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / RAF/MAP kinase cascade / protein autophosphorylation / positive regulation of ERK1 and ERK2 cascade / receptor complex / endosome / positive regulation of cell population proliferation / positive regulation of gene expression / Golgi apparatus / endoplasmic reticulum / extracellular region / ATP binding / plasma membrane
Similarity search - Function
Fibroblast growth factor receptor family / 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 ...Fibroblast growth factor receptor family / 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 / 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
Chem-QS7 / Fibroblast growth factor receptor 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.9 Å
AuthorsLiu, J. / Liu, H.
CitationJournal: Acs Med.Chem.Lett. / Year: 2020
Title: Discovery of Selective, Covalent FGFR4 Inhibitors with Antitumor Activity in Models of Hepatocellular Carcinoma.
Authors: Liu, H. / Niu, D. / Tham Sjin, R.T. / Dubrovskiy, A. / Zhu, Z. / McDonald, J.J. / Fahnoe, K. / Wang, Z. / Munson, M. / Scholte, A. / Barrague, M. / Fitzgerald, M. / Liu, J. / Kothe, M. / ...Authors: Liu, H. / Niu, D. / Tham Sjin, R.T. / Dubrovskiy, A. / Zhu, Z. / McDonald, J.J. / Fahnoe, K. / Wang, Z. / Munson, M. / Scholte, A. / Barrague, M. / Fitzgerald, M. / Liu, J. / Kothe, M. / Sun, F. / Murtie, J. / Ge, J. / Rocnik, J. / Harvey, D. / Ospina, B. / Perron, K. / Zheng, G. / Shehu, E. / D'Agostino, L.A.
History
DepositionDec 13, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 25, 2020Provider: repository / Type: Initial release
Revision 1.1Nov 4, 2020Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Oct 11, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Fibroblast growth factor receptor 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,5804
Polymers33,8671
Non-polymers7123
Water2,972165
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)44.067, 58.670, 60.747
Angle α, β, γ (deg.)90.000, 97.570, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Fibroblast growth factor receptor 4 / FGFR-4


Mass: 33867.207 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: FGFR4, JTK2, TKF / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P22455, receptor protein-tyrosine kinase
#2: Chemical ChemComp-QS7 / N-[(3R,4S)-4-{[6-(2,6-dichloro-3,5-dimethoxyphenyl)-8-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl]amino}oxolan-3-yl]prop-2-enamide


Mass: 520.365 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H23Cl2N5O5 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 165 / 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: 2.3 Å3/Da / Density % sol: 46.45 %
Crystal growTemperature: 277 K / Method: batch mode
Details: 100 mM Bis-Tris pH 5.5, 14% (w/v) polyethylene glycol 3,350, 200 mM lithium sulfate and 2% (w/v) glycerol

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: OXFORD SAPPHIRE CCD / Detector: CCD / Date: Jun 20, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.9→42.02 Å / Num. obs: 24253 / % possible obs: 98.6 % / Redundancy: 3.3 % / Biso Wilson estimate: 32.17 Å2 / Rmerge(I) obs: 0.049 / Net I/σ(I): 13.2
Reflection shellResolution: 1.94→1.99 Å / Rmerge(I) obs: 0.56 / Num. unique obs: 1540

-
Processing

Software
NameVersionClassification
BUSTER2.11.7refinement
Aimlessdata scaling
PDB_EXTRACT3.25data extraction
XDSdata reduction
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3OXZ

3oxz


Resolution: 1.9→42.02 Å / Cor.coef. Fo:Fc: 0.949 / Cor.coef. Fo:Fc free: 0.919 / SU R Cruickshank DPI: 0.154 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.157 / SU Rfree Blow DPI: 0.137 / SU Rfree Cruickshank DPI: 0.136
RfactorNum. reflection% reflectionSelection details
Rfree0.227 1231 5.09 %RANDOM
Rwork0.199 ---
obs0.201 24186 99.1 %-
Displacement parametersBiso max: 121.47 Å2 / Biso mean: 37.4 Å2 / Biso min: 18.45 Å2
Baniso -1Baniso -2Baniso -3
1--0.0989 Å20 Å2-1.187 Å2
2---0.5259 Å20 Å2
3---0.6247 Å2
Refine analyzeLuzzati coordinate error obs: 0.24 Å
Refinement stepCycle: final / Resolution: 1.9→42.02 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2210 0 45 165 2420
Biso mean--36.13 45.29 -
Num. residues----279
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d792SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes378HARMONIC5
X-RAY DIFFRACTIONt_it2310HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion279SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact2752SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d2310HARMONIC20.009
X-RAY DIFFRACTIONt_angle_deg3133HARMONIC20.96
X-RAY DIFFRACTIONt_omega_torsion3.13
X-RAY DIFFRACTIONt_other_torsion15.92
LS refinement shellResolution: 1.9→1.92 Å / Rfactor Rfree error: 0 / Total num. of bins used: 50
RfactorNum. reflection% reflection
Rfree0.3535 23 4.75 %
Rwork0.3143 461 -
all0.3163 484 -
obs--81.09 %
Refinement TLS params.Method: refined / Origin x: 12.5204 Å / Origin y: 3.938 Å / Origin z: 13.1305 Å
111213212223313233
T0.0599 Å2-0.0592 Å2-0.0305 Å2-0.0477 Å20.0254 Å2--0.0504 Å2
L0.5235 °2-0.5356 °20.5046 °2-1.0159 °2-0.3452 °2--1.4389 °2
S-0.0481 Å °0.1297 Å °0.0657 Å °-0.0022 Å °-0.0475 Å °-0.0459 Å °-0.0009 Å °0.0525 Å °0.0956 Å °
Refinement TLS groupSelection details: { A|453 - A|801 }

+
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://pdbjlvh1.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