[English] 日本語
Yorodumi
- PDB-4f64: Crystal structure of Human Fibroblast Growth Factor Receptor 1 Ki... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4f64
TitleCrystal structure of Human Fibroblast Growth Factor Receptor 1 Kinase domain in complex with compound 6
ComponentsFibroblast growth factor receptor 1
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / kinase / ATP binding / phosphorylation / trans-membrane / TRANSFERASE-TRANSFERASE INHIBITOR complex
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 / fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development / diphosphate metabolic process / ventricular zone neuroblast division / vitamin D3 metabolic process / regulation of phosphate transport ...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 / fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development / diphosphate metabolic process / ventricular zone neuroblast division / vitamin D3 metabolic process / regulation of phosphate transport / regulation of lateral mesodermal cell fate specification / FGFR1c and Klotho ligand binding and activation / 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 / auditory receptor cell development / Epithelial-Mesenchymal Transition (EMT) during gastrulation / chordate embryonic development / positive regulation of parathyroid hormone secretion / fibroblast growth factor receptor activity / branching involved in salivary gland morphogenesis / positive regulation of phospholipase activity / mesenchymal cell proliferation / paraxial mesoderm development / lung-associated mesenchyme development / FGFR1b ligand binding and activation / Signaling by activated point mutants of FGFR1 / organ induction / FGFR1c ligand binding and activation / Downstream signaling of activated FGFR1 / Phospholipase C-mediated cascade: FGFR1 / cell projection assembly / cellular response to fibroblast growth factor stimulus / skeletal system morphogenesis / outer ear morphogenesis / positive regulation of mesenchymal cell proliferation / ureteric bud development / middle ear morphogenesis / embryonic limb morphogenesis / inner ear morphogenesis / positive regulation of vascular endothelial cell proliferation / positive regulation of endothelial cell chemotaxis / midbrain development / cardiac muscle cell proliferation / fibroblast growth factor binding / regulation of cell differentiation / positive regulation of stem cell proliferation / PI-3K cascade:FGFR1 / Formation of paraxial mesoderm / phosphatidylinositol-mediated signaling / PI3K Cascade / epithelial to mesenchymal transition / fibroblast growth factor receptor signaling pathway / positive regulation of blood vessel endothelial cell migration / chondrocyte differentiation / calcium ion homeostasis / SHC-mediated cascade:FGFR1 / positive regulation of cardiac muscle cell proliferation / cell maturation / FRS-mediated FGFR1 signaling / positive regulation of neuron differentiation / Signaling by FGFR1 in disease / NCAM signaling for neurite out-growth / SH2 domain binding / stem cell proliferation / Signal transduction by L1 / skeletal system development / stem cell differentiation / positive regulation of cell differentiation / sensory perception of sound / Negative regulation of FGFR1 signaling / positive regulation of MAP kinase activity / neuron migration / receptor protein-tyrosine kinase / positive regulation of neuron projection development / peptidyl-tyrosine phosphorylation / Constitutive Signaling by Aberrant PI3K in Cancer / MAPK cascade / neuron projection development / cell migration / PIP3 activates AKT signaling / heparin binding / gene expression / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / RAF/MAP kinase cascade / cytoplasmic vesicle / protein tyrosine kinase activity / angiogenesis / in utero embryonic development / protein autophosphorylation / positive regulation of MAPK cascade / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor complex / protein phosphorylation / positive regulation of cell population proliferation / negative regulation of transcription by RNA polymerase II / protein homodimerization activity / extracellular region
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. / Tyrosine-protein kinase, active site / Immunoglobulin subtype / Immunoglobulin / 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-0S8 / Fibroblast growth factor receptor 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.05 Å
AuthorsNorman, R.A. / Breed, J. / Ogg, D.
CitationJournal: J.Med.Chem. / Year: 2012
Title: Protein-Ligand Crystal Structures Can Guide the Design of Selective Inhibitors of the FGFR Tyrosine Kinase.
Authors: Norman, R.A. / Schott, A.K. / Andrews, D.M. / Breed, J. / Foote, K.M. / Garner, A.P. / Ogg, D. / Orme, J.P. / Pink, J.H. / Roberts, K. / Rudge, D.A. / Thomas, A.P. / Leach, A.G.
History
DepositionMay 14, 2012Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 6, 2012Provider: repository / Type: Initial release
Revision 1.1Jun 27, 2012Group: Database references
Revision 1.2Sep 13, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / 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

-
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)71,4609
Polymers70,2712
Non-polymers1,1897
Water3,891216
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)208.810, 57.277, 65.433
Angle α, β, γ (deg.)90.00, 107.55, 90.00
Int Tables number5
Space group name H-MC121

-
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: 35135.340 Da / Num. of mol.: 2 / Fragment: kinase domain (UNP residues 458-765) / Mutation: C488A, C584S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: FGFR1, BFGFR, CEK, FGFBR, FLG, FLT2, HBGFR / Production host: Escherichia coli (E. coli)
References: UniProt: P11362, receptor protein-tyrosine kinase
#2: Chemical ChemComp-0S8 / 5-bromo-N~4~-[3-(3-methoxypropyl)-1H-pyrazol-5-yl]-N~2~-[(3-methyl-1,2-oxazol-5-yl)methyl]pyrimidine-2,4-diamine


Mass: 422.280 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C16H20BrN7O2
#3: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C2H6O2
#4: Chemical ChemComp-SO4 / SULFATE ION


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


Mass: 18.015 Da / Num. of mol.: 216 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.65 Å3/Da / Density % sol: 53.66 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop
Details: 16-20% PEG8000, 100 mM PCTP, 100-300 mM ammonium sulfate, 25% ethylene glycol, pH 6.25-7.25, VAPOR DIFFUSION, HANGING DROP, temperature 277K
PH range: 6.25-7.25

-
Data collection

DiffractionMean temperature: 110 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU MICROMAX-007 / Wavelength: 1.54 Å
DetectorType: RIGAKU SATURN 92 / Detector: CCD / Date: Dec 23, 2004
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54 Å / Relative weight: 1
ReflectionResolution: 2.05→61.931 Å / Num. all: 46555 / Num. obs: 44839 / % possible obs: 96.75 % / Observed criterion σ(F): 1 / Observed criterion σ(I): 1 / Redundancy: 2.7 % / Rmerge(I) obs: 0.149 / Rsym value: 0.128 / Net I/σ(I): 6.6
Reflection shellResolution: 2.05→2.16 Å / Redundancy: 2.7 % / Rmerge(I) obs: 0.572 / Mean I/σ(I) obs: 2.2 / Rsym value: 0.504 / % possible all: 96.06

-
Processing

Software
NameVersionClassification
CrystalCleardata collection
AMoREphasing
REFMAC5.2.0005refinement
MOSFLMdata reduction
SCALAdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1FGK

1fgk


Resolution: 2.05→61.9 Å / Cor.coef. Fo:Fc: 0.933 / Cor.coef. Fo:Fc free: 0.885 / SU B: 13.472 / SU ML: 0.157 / Cross valid method: THROUGHOUT / ESU R: 0.198 / ESU R Free: 0.187 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.26912 2248 5.1 %RANDOM
Rwork0.21426 ---
obs0.21701 42144 95.36 %-
all-44839 --
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 26.505 Å2
Baniso -1Baniso -2Baniso -3
1--2.11 Å20 Å2-0.96 Å2
2--3.77 Å20 Å2
3----2.24 Å2
Refinement stepCycle: LAST / Resolution: 2.05→61.9 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4229 0 73 216 4518
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0140.0224411
X-RAY DIFFRACTIONr_bond_other_d0.0060.024067
X-RAY DIFFRACTIONr_angle_refined_deg1.4031.9915974
X-RAY DIFFRACTIONr_angle_other_deg0.83139388
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.7955547
X-RAY DIFFRACTIONr_dihedral_angle_2_deg36.05423.699173
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.37215732
X-RAY DIFFRACTIONr_dihedral_angle_4_deg15.7221528
X-RAY DIFFRACTIONr_chiral_restr0.0870.2673
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.024821
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02845
X-RAY DIFFRACTIONr_nbd_refined0.2040.2865
X-RAY DIFFRACTIONr_nbd_other0.1940.23871
X-RAY DIFFRACTIONr_nbtor_refined0.1760.22117
X-RAY DIFFRACTIONr_nbtor_other0.0840.22318
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1590.2201
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.0820.27
X-RAY DIFFRACTIONr_symmetry_vdw_other0.2930.238
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.1450.211
X-RAY DIFFRACTIONr_mcbond_it0.9151.52874
X-RAY DIFFRACTIONr_mcbond_other0.4591.51113
X-RAY DIFFRACTIONr_mcangle_it1.24524417
X-RAY DIFFRACTIONr_scbond_it2.4531829
X-RAY DIFFRACTIONr_scangle_it3.1494.51557
LS refinement shellResolution: 2.05→2.103 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.389 149 -
Rwork0.315 3028 -
obs--93.77 %
Refinement TLS params.Method: refined / Origin x: 58.2529 Å / Origin y: -0.0891 Å / Origin z: 16.3069 Å
111213212223313233
T0.0011 Å20.0121 Å20.0011 Å2--0.0588 Å20.018 Å2---0.0426 Å2
L1.7038 °2-0.3742 °20.0031 °2-0.1372 °20.0522 °2--0.0605 °2
S0.1083 Å °0.1982 Å °0.0041 Å °-0.0267 Å °-0.0834 Å °0.0344 Å °-0.0028 Å °0.0159 Å °-0.0249 Å °
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A464 - 762
2X-RAY DIFFRACTION1B461 - 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