[English] 日本語
Yorodumi
- PDB-5xfj: Crystal structure of LY2874455 in complex of FGFR4 gatekeeper mut... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5xfj
TitleCrystal structure of LY2874455 in complex of FGFR4 gatekeeper mutation (V550M)
ComponentsFibroblast growth factor receptor 4
KeywordsTRANSFERASE / inhibitor / kinase / gatekeeper / mutation
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 / cell surface receptor protein tyrosine kinase signaling pathway / Constitutive Signaling by Aberrant PI3K in Cancer / cell migration / glucose homeostasis / PIP3 activates AKT signaling / 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 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Ig-like domain profile. / Immunoglobulin-like domain / Phosphorylase Kinase; 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
Chem-6LF / Fibroblast growth factor receptor 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 3.25 Å
AuthorsWu, D. / Chen, Y.
Funding support China, 3items
OrganizationGrant numberCountry
National Natural Science Foundation of China81372904 China
National Natural Science Foundation of China81570537 China
National Natural Science Foundation of China81272971 China
CitationJournal: Chem. Commun. (Camb.) / Year: 2018
Title: LY2874455 potently inhibits FGFR gatekeeper mutants and overcomes mutation-based resistance.
Authors: Wu, D. / Guo, M. / Min, X. / Dai, S. / Li, M. / Tan, S. / Li, G. / Chen, X. / Ma, Y. / Li, J. / Jiang, L. / Qu, L. / Zhou, Z. / Chen, Z. / Chen, L. / Xu, G. / Chen, Y.
History
DepositionApr 10, 2017Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Aug 8, 2018Provider: repository / Type: Initial release
Revision 1.1Aug 15, 2018Group: Data collection / Category: reflns / Item: _reflns.number_obs
Revision 1.2Feb 20, 2019Group: Data collection / 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 1.3Mar 27, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2
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)35,1672
Polymers34,7231
Non-polymers4441
Water0
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area13890 Å2
Unit cell
Length a, b, c (Å)62.216, 62.216, 184.955
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number96
Space group name H-MP43212

-
Components

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


Mass: 34723.137 Da / Num. of mol.: 1 / Fragment: UNP residues 445-753 / Mutation: V550M
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: FGFR4, JTK2, TKF / Production host: Escherichia coli (E. coli)
References: UniProt: P22455, receptor protein-tyrosine kinase
#2: Chemical ChemComp-6LF / 2-[4-[E-2-[5-[(1R)-1-[3,5-bis(chloranyl)pyridin-4-yl]ethoxy]-1H-indazol-3-yl]ethenyl]pyrazol-1-yl]ethanol / LY2874455


Mass: 444.314 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C21H19Cl2N5O2

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.58 Å3/Da / Density % sol: 52.28 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / Details: 0.65M NH2H2PO4

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL17U / Wavelength: 1.54178 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Dec 28, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54178 Å / Relative weight: 1
ReflectionResolution: 3.25→39.73 Å / Num. obs: 6209 / % possible obs: 99.3 % / Redundancy: 22.2 % / Net I/σ(I): 19.18

-
Processing

Software
NameVersionClassification
PHENIX1.11.1_2575refinement
HKL-3000data collection
HKL-3000data reduction
PHENIXphasing
RefinementResolution: 3.25→39.727 Å / SU ML: 0.4 / Cross valid method: NONE / σ(F): 1.34 / Phase error: 40.46
RfactorNum. reflection% reflection
Rfree0.3363 613 10 %
Rwork0.2787 --
obs0.2845 6130 98.03 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Refinement stepCycle: LAST / Resolution: 3.25→39.727 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2104 0 30 0 2134
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0052190
X-RAY DIFFRACTIONf_angle_d0.9672970
X-RAY DIFFRACTIONf_dihedral_angle_d15.1781322
X-RAY DIFFRACTIONf_chiral_restr0.047322
X-RAY DIFFRACTIONf_plane_restr0.006381
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
3.2463-3.57270.39861460.31731312X-RAY DIFFRACTION97
3.5727-4.08930.39411460.31181320X-RAY DIFFRACTION96
4.0893-5.15030.34431560.27271396X-RAY DIFFRACTION100
5.1503-39.73010.30271650.26321489X-RAY DIFFRACTION99

+
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