[English] 日本語
Yorodumi
- PDB-3dpk: cFMS tyrosine kinase in complex with a pyridopyrimidinone inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3dpk
TitlecFMS tyrosine kinase in complex with a pyridopyrimidinone inhibitor
ComponentsMacrophage colony-stimulating factor 1 receptor, Fibroblast growth factor receptor 1
KeywordsTRANSFERASE / RECEPTOR TYROSINE KINASE / KINASE-INHIBITOR COMPLEX / ATP-binding / Glycoprotein / Immunoglobulin domain / Kinase / Membrane / Nucleotide-binding / Phosphoprotein / Proto-oncogene / Receptor / Transmembrane / Tyrosine-protein kinase / Craniosynostosis / Disease mutation / Dwarfism / Heparin-binding / Kallmann syndrome
Function / homology
Function and homology information


forebrain neuron differentiation / macrophage colony-stimulating factor receptor activity / CSF1-CSF1R complex / macrophage colony-stimulating factor signaling pathway / regulation of macrophage migration / 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 ...forebrain neuron differentiation / macrophage colony-stimulating factor receptor activity / CSF1-CSF1R complex / macrophage colony-stimulating factor signaling pathway / regulation of macrophage migration / 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 / cellular response to macrophage colony-stimulating factor stimulus / regulation of phosphate transport / FGFR1c and Klotho ligand binding and activation / cell-cell junction maintenance / 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 / microglial cell proliferation / receptor-receptor interaction / chordate embryonic development / positive regulation of parathyroid hormone secretion / auditory receptor cell development / mesenchymal cell proliferation / paraxial mesoderm development / olfactory bulb development / mammary gland duct morphogenesis / 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 / host-mediated activation of viral process / cell projection assembly / ruffle organization / positive regulation of macrophage proliferation / outer ear morphogenesis / embryonic limb morphogenesis / regulation of bone resorption / 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 / positive regulation of cell motility / Other interleukin signaling / positive regulation of tyrosine phosphorylation of STAT protein / inner ear morphogenesis / growth factor binding / positive regulation of protein tyrosine kinase activity / phosphatidylinositol-mediated signaling / PI-3K cascade:FGFR1 / positive regulation of stem cell proliferation / Formation of paraxial mesoderm / positive regulation of macrophage chemotaxis / midbrain development / cytokine binding / cellular response to cytokine stimulus / fibroblast growth factor binding / positive regulation of MAP kinase activity / regulation of cell differentiation / regulation of MAPK cascade / hemopoiesis / Transcriptional Regulation by VENTX / macrophage differentiation / monocyte 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 / positive regulation of chemokine production / 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 / axon guidance / cell surface receptor protein tyrosine kinase signaling pathway / osteoclast differentiation / peptidyl-tyrosine phosphorylation
Similarity search - Function
Macrophage colony-stimulating factor 1 receptor / Platelet-derived growth factor receptor Ig-like domain 4 / Fibroblast growth factor receptor 1, catalytic domain / Tyrosine-protein kinase, receptor class III, conserved site / Receptor tyrosine kinase class III signature. / Fibroblast growth factor receptor family / Immunoglobulin / Immunoglobulin domain / Immunoglobulin I-set / Immunoglobulin I-set domain ...Macrophage colony-stimulating factor 1 receptor / Platelet-derived growth factor receptor Ig-like domain 4 / Fibroblast growth factor receptor 1, catalytic domain / Tyrosine-protein kinase, receptor class III, conserved site / Receptor tyrosine kinase class III signature. / 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-8C5 / Macrophage colony-stimulating factor 1 receptor / Fibroblast growth factor receptor 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.95 Å
AuthorsSchubert, C.
CitationJournal: J.Med.Chem. / Year: 2009
Title: Pyrido[2,3-d]pyrimidin-5-ones: a novel class of antiinflammatory macrophage colony-stimulating factor-1 receptor inhibitors
Authors: Huang, H. / Hutta, D.A. / Rinker, J.M. / Hu, H. / Parsons, W.H. / Schubert, C. / DesJarlais, R.L. / Crysler, C.S. / Chaikin, M.A. / Donatelli, R.R. / Chen, Y. / Cheng, D. / Zhou, Z. / ...Authors: Huang, H. / Hutta, D.A. / Rinker, J.M. / Hu, H. / Parsons, W.H. / Schubert, C. / DesJarlais, R.L. / Crysler, C.S. / Chaikin, M.A. / Donatelli, R.R. / Chen, Y. / Cheng, D. / Zhou, Z. / Yurkow, E. / Manthey, C.L. / Player, M.R.
History
DepositionJul 8, 2008Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 17, 2009Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Jan 25, 2017Group: Database references / Source and taxonomy
Revision 1.3Jul 26, 2017Group: Source and taxonomy / Category: entity_src_gen
Revision 1.4Oct 25, 2017Group: Refinement description / Category: software
Revision 1.5Aug 30, 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: Macrophage colony-stimulating factor 1 receptor, Fibroblast growth factor receptor 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,8435
Polymers38,0641
Non-polymers7794
Water2,216123
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)80.950, 80.950, 145.420
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number146
Space group name H-MH3

-
Components

#1: Protein Macrophage colony-stimulating factor 1 receptor, Fibroblast growth factor receptor 1 / CSF-1 receptor / CSF-1-R / CSF-1R / M-CSF-R / Proto-oncogene c-Fms / FGFR-1 / Basic fibroblast ...CSF-1 receptor / CSF-1-R / CSF-1R / M-CSF-R / Proto-oncogene c-Fms / 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: 38064.477 Da / Num. of mol.: 1 / Fragment: KINASE DOMAIN
Mutation: Native kinase insert domain replaced by FGF receptor kinase insert domain
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human)
Gene: CSF1R, FGFBR, FGFR1, FLG, FLT2, FMS, BFGFR, CEK, HBGFR
Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P07333, UniProt: P11362, receptor protein-tyrosine kinase
#2: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: SO4
#3: Chemical ChemComp-8C5 / 8-cyclohexyl-N-methoxy-5-oxo-2-{[4-(2-pyrrolidin-1-ylethyl)phenyl]amino}-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxamide


Mass: 490.597 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C27H34N6O3
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 123 / 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: 2.41 Å3/Da / Density % sol: 48.94 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 5.2
Details: PEG 3350, SODIUM ACETATE, LI2SO4, pH 5.2, VAPOR DIFFUSION, HANGING DROP, temperature 298K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 210 / Detector: CCD / Date: Nov 19, 2005
RadiationMonochromator: SAGITALLY FOCUSED Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.8→50 Å / Num. all: 27585 / Num. obs: 27585 / % possible obs: 83.8 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 3.6 % / Rmerge(I) obs: 0.093 / Net I/σ(I): 12.2
Reflection shellResolution: 1.8→1.86 Å / Redundancy: 3.6 % / Rmerge(I) obs: 0.276 / Mean I/σ(I) obs: 4.3 / Num. unique all: 3289 / % possible all: 99.6

-
Processing

Software
NameVersionClassification
PHENIX(phenix.refine)refinement
HKL-2000data reduction
HKL-2000data scaling
CNXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2i1m

2i1m


Resolution: 1.95→34.1 Å / Isotropic thermal model: isotropic / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber
Details: Isotropic B-factor refinement for non-hydrogen atoms. Hydrogens were assigned the B-factor of their "parent" atom and one B-factor for all hydrogens was refined, as implemented in phenix
RfactorNum. reflection% reflectionSelection details
Rfree0.2441 2172 9.85 %Random
Rwork0.1862 ---
all0.192 22043 --
obs0.192 22043 85 %-
Displacement parametersBiso mean: 28.61 Å2
Refinement stepCycle: LAST / Resolution: 1.95→34.1 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2208 0 51 123 2382
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONf_bond_d0.01
X-RAY DIFFRACTIONf_angle_deg1.018
X-RAY DIFFRACTIONf_improper_angle_d0.076
X-RAY DIFFRACTIONf_dihedral_angle_d17.4
X-RAY DIFFRACTIONf_planarity_d0.009

+
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