[English] 日本語
Yorodumi
- PDB-5ur1: FGFR1 kinase domain complex with SN37333 in reversible binding mode -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5ur1
TitleFGFR1 kinase domain complex with SN37333 in reversible binding mode
ComponentsFibroblast growth factor receptor 1
Keywordstransferase/transferase inhibitor / transferase / 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 / 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 / auditory receptor cell development / fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development / ventricular zone neuroblast division / Epithelial-Mesenchymal Transition (EMT) during gastrulation / 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 / positive regulation of phospholipase activity / lung-associated mesenchyme development / cell projection assembly / outer ear morphogenesis / embryonic limb morphogenesis / positive regulation of vascular endothelial cell proliferation / positive regulation of endothelial cell chemotaxis / skeletal system morphogenesis / positive regulation of mesenchymal cell proliferation / middle ear morphogenesis / ureteric bud development / cardiac muscle cell proliferation / inner ear morphogenesis / phosphatidylinositol-mediated signaling / PI-3K cascade:FGFR1 / midbrain development / positive regulation of stem cell proliferation / Formation of paraxial mesoderm / fibroblast growth factor binding / regulation of cell differentiation / PI3K Cascade / cellular response to fibroblast growth factor stimulus / positive regulation of blood vessel endothelial cell migration / fibroblast growth factor receptor signaling pathway / epithelial to mesenchymal transition / chondrocyte differentiation / SHC-mediated cascade:FGFR1 / calcium ion homeostasis / cell maturation / positive regulation of cardiac muscle cell proliferation / FRS-mediated FGFR1 signaling / Signaling by FGFR1 in disease / NCAM signaling for neurite out-growth / positive regulation of MAP kinase activity / positive regulation of neuron differentiation / SH2 domain binding / Signal transduction by L1 / stem cell proliferation / skeletal system development / positive regulation of cell differentiation / stem cell differentiation / sensory perception of sound / Negative regulation of FGFR1 signaling / placental growth factor receptor activity / insulin receptor activity / vascular endothelial growth factor receptor activity / hepatocyte growth factor receptor activity / macrophage colony-stimulating factor receptor activity / platelet-derived growth factor alpha-receptor activity / platelet-derived growth factor beta-receptor activity / stem cell factor receptor activity / boss receptor activity / protein tyrosine kinase collagen receptor activity / brain-derived neurotrophic factor receptor activity / transmembrane-ephrin receptor activity / GPI-linked ephrin receptor activity / epidermal growth factor receptor activity / fibroblast growth factor receptor activity / insulin-like growth factor receptor activity / receptor protein-tyrosine kinase / peptidyl-tyrosine phosphorylation / 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
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 / Phosphorylase Kinase; domain 1 / Ig-like domain profile. / Immunoglobulin-like domain / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Immunoglobulin-like domain superfamily / Transferase(Phosphotransferase); domain 1 / 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-YY9 / Fibroblast growth factor receptor 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.2 Å
AuthorsYosaatmadja, Y. / Paik, W.-K. / Smaill, J.B. / Squire, C.J.
CitationJournal: Eur J Med Chem / Year: 2017
Title: 2-Oxo-3, 4-dihydropyrimido[4, 5-d]pyrimidinyl derivatives as new irreversible pan fibroblast growth factor receptor (FGFR) inhibitors.
Authors: Li, X. / Guise, C.P. / Taghipouran, R. / Yosaatmadja, Y. / Ashoorzadeh, A. / Paik, W.K. / Squire, C.J. / Jiang, S. / Luo, J. / Xu, Y. / Tu, Z.C. / Lu, X. / Ren, X. / Patterson, A.V. / Smaill, J.B. / Ding, K.
History
DepositionFeb 9, 2017Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 31, 2017Provider: 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)71,9884
Polymers70,7072
Non-polymers1,2812
Water93752
1
A: Fibroblast growth factor receptor 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,9942
Polymers35,3541
Non-polymers6411
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)35,9942
Polymers35,3541
Non-polymers6411
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)213.050, 51.783, 66.070
Angle α, β, γ (deg.)90.00, 106.87, 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 / 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-YY9 / 3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-{1-[4-(dimethylamino)but-2-enoyl]piperidin-4-yl}-7-(phenylamino)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one


Mass: 640.560 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C31H35Cl2N7O4
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 52 / 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: 2.47 Å3/Da / Density % sol: 50.13 %
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: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Australian Synchrotron / Beamline: MX1 / Wavelength: 0.9537 Å
DetectorType: ADSC QUANTUM 210r / Detector: CCD / Date: Aug 24, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9537 Å / Relative weight: 1
ReflectionResolution: 2.2→19.54 Å / Num. obs: 35322 / % possible obs: 99.8 % / Redundancy: 14.9 % / CC1/2: 0.999 / Rmerge(I) obs: 0.154 / Rpim(I) all: 0.041 / Net I/σ(I): 18.4
Reflection shellResolution: 2.2→2.27 Å / Redundancy: 15 % / Mean I/σ(I) obs: 2.4 / Num. unique all: 3440 / Num. unique obs: 3248 / CC1/2: 0.736 / Rpim(I) all: 0.349 / % 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: 2.2→19.54 Å / Cor.coef. Fo:Fc: 0.938 / Cor.coef. Fo:Fc free: 0.905 / SU B: 17.593 / SU ML: 0.192 / Cross valid method: THROUGHOUT / ESU R: 0.261 / ESU R Free: 0.222 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.27658 1758 5 %RANDOM
Rwork0.22715 ---
obs0.2296 33557 99.71 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 41.735 Å2
Baniso -1Baniso -2Baniso -3
1--0.29 Å20 Å20.38 Å2
2--0.42 Å2-0 Å2
3----0.3 Å2
Refinement stepCycle: 1 / Resolution: 2.2→19.54 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4161 0 79 52 4292
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0090.0194341
X-RAY DIFFRACTIONr_bond_other_d0.0010.024109
X-RAY DIFFRACTIONr_angle_refined_deg1.3831.9995893
X-RAY DIFFRACTIONr_angle_other_deg0.7823.0049449
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.7725537
X-RAY DIFFRACTIONr_dihedral_angle_2_deg37.23824.302172
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.03415725
X-RAY DIFFRACTIONr_dihedral_angle_4_deg13.8391525
X-RAY DIFFRACTIONr_chiral_restr0.0930.2659
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.0214841
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02912
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_it1.2292.6022169
X-RAY DIFFRACTIONr_mcbond_other1.2292.6012168
X-RAY DIFFRACTIONr_mcangle_it2.0473.892699
X-RAY DIFFRACTIONr_mcangle_other2.0473.892700
X-RAY DIFFRACTIONr_scbond_it1.2572.6262172
X-RAY DIFFRACTIONr_scbond_other1.2572.6262173
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other2.0423.8973194
X-RAY DIFFRACTIONr_long_range_B_refined3.41920.0974845
X-RAY DIFFRACTIONr_long_range_B_other3.40820.0984837
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.2→2.257 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.37 129 -
Rwork0.341 2448 -
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)
12.2636-0.09750.79940.8855-0.68913.33930.0484-0.0699-0.10020.0434-0.02590.06110.16310.017-0.02250.04170.01070.01180.1642-0.00920.0126-18.3399-8.79183.877
21.8751-0.46461.45491.0153-0.87543.40120.0014-0.2910.00550.13810.01460.0506-0.013-0.0448-0.0160.11490.01390.0210.0751-0.00630.0579-46.643915.216422.4498
313.1-12.0555-10.188113.19689.40327.9246-0.35950.6434-1.34890.4286-0.68071.21060.2904-0.50411.04020.22790.0434-0.03230.2946-0.03540.1712-32.5603-0.479922.2666
40.6473-0.1845-0.35080.27960.00320.28570.01050.00530.03010.0259-0.02370.0109-0.05980.10670.01320.1061-0.0415-0.03730.21220.03220.0203-32.50715.38267.5995
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A464 - 765
2X-RAY DIFFRACTION2B464 - 763
3X-RAY DIFFRACTION3A801
4X-RAY DIFFRACTION3B801
5X-RAY DIFFRACTION4A901 - 928
6X-RAY DIFFRACTION4B901 - 924

+
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