[English] 日本語
Yorodumi
- PDB-6c18: FGFR1 kinase complex with inhibitor SN37115 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6c18
TitleFGFR1 kinase complex with inhibitor SN37115
ComponentsFibroblast growth factor receptor 1
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / Kinase / 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 / diphosphate metabolic process / Signaling by plasma membrane FGFR1 fusions / regulation of phosphate transport / FGFR1c and Klotho ligand binding and activation / regulation of lateral mesodermal cell fate specification / positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway ...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 / diphosphate metabolic process / Signaling by plasma membrane FGFR1 fusions / regulation of phosphate transport / FGFR1c and Klotho ligand binding and activation / regulation of lateral mesodermal cell fate specification / positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway / vitamin D3 metabolic process / cementum mineralization / regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling / 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 / positive regulation of phospholipase activity / receptor-receptor interaction / chordate embryonic development / positive regulation of parathyroid hormone secretion / auditory receptor cell development / mesenchymal cell proliferation / paraxial mesoderm development / FGFR1b ligand binding and activation / regulation of postsynaptic density assembly / Signaling by activated point mutants of FGFR1 / fibroblast growth factor receptor activity / 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 / middle ear morphogenesis / skeletal system morphogenesis / inner ear morphogenesis / phosphatidylinositol-mediated signaling / PI-3K cascade:FGFR1 / positive regulation of stem cell proliferation / Formation of paraxial mesoderm / midbrain development / fibroblast growth factor binding / positive regulation of MAP kinase activity / 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 / cardiac muscle cell proliferation / calcium ion homeostasis / SHC-mediated cascade:FGFR1 / positive regulation of cardiac muscle cell proliferation / cell maturation / FRS-mediated FGFR1 signaling / cellular response to fibroblast growth factor stimulus / positive regulation of neuron differentiation / Signaling by FGFR1 in disease / NCAM signaling for neurite out-growth / SH2 domain binding / peptidyl-tyrosine phosphorylation / stem cell proliferation / Signal transduction by L1 / skeletal system development / stem cell differentiation / positive regulation of cell differentiation / Negative regulation of FGFR1 signaling / sensory perception of sound / positive regulation of neuron projection development / receptor protein-tyrosine kinase / neuron migration / neuron projection development / Constitutive Signaling by Aberrant PI3K in Cancer / cell migration / PIP3 activates AKT signaling / MAPK cascade / heparin binding / protein autophosphorylation / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / RAF/MAP kinase cascade / cytoplasmic vesicle / protein tyrosine kinase activity / angiogenesis / gene expression / in utero embryonic development / protein phosphorylation / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor complex / postsynapse / positive regulation of MAPK cascade / 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 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); 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-YY5 / Fibroblast growth factor receptor 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.3 Å
AuthorsYosaatmadja, Y. / Smaill, J.B. / Squire, C.J.
Funding support New Zealand, 1items
OrganizationGrant numberCountry
Health REsearch Council of New ZEaland New Zealand
CitationJournal: To Be Published
Title: Understanding the structural requirements for covalent inhibition of FGFR1-3
Authors: Yosaatmadja, Y. / Squire, C.J. / Patterson, A.V. / Smaill, J.B.
History
DepositionJan 4, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 16, 2019Provider: repository / Type: Initial release
Revision 1.1Oct 4, 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 1
B: Fibroblast growth factor receptor 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)71,9885
Polymers70,7072
Non-polymers1,2813
Water30617
1
A: Fibroblast growth factor receptor 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,0423
Polymers35,3541
Non-polymers6892
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Fibroblast growth factor receptor 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,9462
Polymers35,3541
Non-polymers5931
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)208.962, 49.837, 65.085
Angle α, β, γ (deg.)90.00, 106.19, 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 / bFGF-R-1 / Fms-like tyrosine kinase 2 / FLT-2 ...FGFR-1 / Basic fibroblast growth factor receptor 1 / bFGF-R-1 / Fms-like tyrosine kinase 2 / FLT-2 / N-sam / Proto-oncogene c-Fgr


Mass: 35353.613 Da / Num. of mol.: 2 / Fragment: UNP residues 457-763 / Mutation: C486A, C582S
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-YY5 / 3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-{(3S)-1-[(2E)-4-(dimethylamino)but-2-enoyl]pyrrolidin-3-yl}-7-[(propan-2-yl)amino]-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one


Mass: 592.517 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C27H35Cl2N7O4
#3: Chemical ChemComp-SO4 / SULFATE ION


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


Mass: 18.015 Da / Num. of mol.: 17 / 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: 2.3 Å3/Da / Density % sol: 46.56 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop
Details: 20% MPEG 5000, 0.1 M sodium cacodylate pH 7.5, 0.2 M ammonium sulfate

-
Data collection

DiffractionMean temperature: 110 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU MICROMAX-007 HF / Wavelength: 1.5418 Å
DetectorType: MAR scanner 345 mm plate / Detector: IMAGE PLATE / Date: Jan 24, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 2.3→19.78 Å / Num. obs: 28937 / % possible obs: 99.8 % / Redundancy: 7.4 % / CC1/2: 0.997 / Rmerge(I) obs: 0.142 / Rpim(I) all: 0.06 / Net I/σ(I): 11.8
Reflection shellResolution: 2.3→2.38 Å / Redundancy: 7.3 % / Mean I/σ(I) obs: 1.5 / Num. unique all: 2836 / Num. unique obs: 2836 / CC1/2: 0.599 / Rpim(I) all: 0.612 / % possible all: 100

-
Processing

Software
NameVersionClassification
REFMAC5.8.0049refinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4WUN

4wun


Resolution: 2.3→19.78 Å / Cor.coef. Fo:Fc: 0.939 / Cor.coef. Fo:Fc free: 0.912 / SU B: 20.985 / SU ML: 0.232 / Cross valid method: THROUGHOUT / ESU R: 0.332 / ESU R Free: 0.245 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.26668 1377 4.8 %RANDOM
Rwork0.22269 ---
obs0.22481 27539 99.72 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso mean: 44.145 Å2
Baniso -1Baniso -2Baniso -3
1-0.18 Å2-0 Å20.8 Å2
2---1.31 Å2-0 Å2
3---0.57 Å2
Refinement stepCycle: 1 / Resolution: 2.3→19.78 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4096 0 83 17 4196
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0110.0194332
X-RAY DIFFRACTIONr_bond_other_d0.0020.024109
X-RAY DIFFRACTIONr_angle_refined_deg1.5091.9955890
X-RAY DIFFRACTIONr_angle_other_deg0.8583.0049446
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.4785537
X-RAY DIFFRACTIONr_dihedral_angle_2_deg38.93124.343175
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.51215719
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.911525
X-RAY DIFFRACTIONr_chiral_restr0.1040.2664
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.0214829
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02914
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_it1.5542.6642157
X-RAY DIFFRACTIONr_mcbond_other1.5512.6632156
X-RAY DIFFRACTIONr_mcangle_it2.5983.9862688
X-RAY DIFFRACTIONr_mcangle_other2.5993.9872689
X-RAY DIFFRACTIONr_scbond_it1.7712.8632175
X-RAY DIFFRACTIONr_scbond_other1.7662.8572172
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other2.9234.2113196
X-RAY DIFFRACTIONr_long_range_B_refined4.50321.5114857
X-RAY DIFFRACTIONr_long_range_B_other4.50221.5154856
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.3→2.36 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.36 96 -
Rwork0.31 2035 -
obs--100 %
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)
12.0906-0.21650.82041.0508-0.69053.86880.09190.0032-0.11670.0487-0.02460.10370.21790.0211-0.06740.0417-0.0267-0.01080.12780.01410.0236-18.577616.81773.7057
22.0772-0.48891.47711.5045-0.83053.17390.0025-0.13820.05170.1490.01960.0777-0.0543-0.065-0.0220.07520.0084-0.03080.1821-0.01320.0354-44.825340.639222.275
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A465 - 765
2X-RAY DIFFRACTION2B466 - 762

+
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