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Open data
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Basic information
Entry | Database: PDB / ID: 8swe | ||||||
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Title | FGFR2 Kinase Domain Bound to Reversible Inhibitor Cmpd 3 | ||||||
![]() | Fibroblast growth factor receptor 2 | ||||||
![]() | ONCOPROTEIN / Inhibitor Kinase | ||||||
Function / homology | ![]() Signaling by FGFR2 amplification mutants / Signaling by FGFR2 fusions / fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow cell / fibroblast growth factor receptor signaling pathway involved in hemopoiesis / fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow / fibroblast growth factor receptor signaling pathway involved in mammary gland specification / lateral sprouting from an epithelium / mammary gland bud formation / branch elongation involved in salivary gland morphogenesis / mesenchymal cell differentiation involved in lung development ...Signaling by FGFR2 amplification mutants / Signaling by FGFR2 fusions / fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow cell / fibroblast growth factor receptor signaling pathway involved in hemopoiesis / fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow / fibroblast growth factor receptor signaling pathway involved in mammary gland specification / lateral sprouting from an epithelium / mammary gland bud formation / branch elongation involved in salivary gland morphogenesis / mesenchymal cell differentiation involved in lung development / lacrimal gland development / otic vesicle formation / prostate gland morphogenesis / regulation of smooth muscle cell differentiation / orbitofrontal cortex development / regulation of morphogenesis of a branching structure / squamous basal epithelial stem cell differentiation involved in prostate gland acinus development / branching morphogenesis of a nerve / embryonic organ morphogenesis / endochondral bone growth / morphogenesis of embryonic epithelium / epidermis morphogenesis / bud elongation involved in lung branching / positive regulation of epithelial cell proliferation involved in lung morphogenesis / pyramidal neuron development / membranous septum morphogenesis / reproductive structure development / limb bud formation / lung lobe morphogenesis / gland morphogenesis / fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development / ventricular zone neuroblast division / embryonic digestive tract morphogenesis / epithelial cell proliferation involved in salivary gland morphogenesis / mesenchymal cell differentiation / branching involved in prostate gland morphogenesis / mesenchymal cell proliferation involved in lung development / branching involved in labyrinthine layer morphogenesis / FGFR2b ligand binding and activation / FGFR2c ligand binding and activation / Activated point mutants of FGFR2 / regulation of osteoblast proliferation / Phospholipase C-mediated cascade; FGFR2 / fibroblast growth factor receptor activity / embryonic pattern specification / branching involved in salivary gland morphogenesis / outflow tract septum morphogenesis / positive regulation of phospholipase activity / lung-associated mesenchyme development / mesodermal cell differentiation / regulation of smoothened signaling pathway / embryonic cranial skeleton morphogenesis / digestive tract development / bone morphogenesis / skeletal system morphogenesis / odontogenesis / positive regulation of mesenchymal cell proliferation / ventricular cardiac muscle tissue morphogenesis / ureteric bud development / regulation of osteoblast differentiation / Signaling by FGFR2 IIIa TM / midbrain development / organ growth / inner ear morphogenesis / hair follicle morphogenesis / lung alveolus development / prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis / fibroblast growth factor binding / PI-3K cascade:FGFR2 / bone mineralization / prostate epithelial cord elongation / positive regulation of cell division / excitatory synapse / PI3K Cascade / positive regulation of Wnt signaling pathway / negative regulation of keratinocyte proliferation / epithelial to mesenchymal transition / fibroblast growth factor receptor signaling pathway / cell fate commitment / embryonic organ development / positive regulation of cell cycle / SHC-mediated cascade:FGFR2 / cellular response to retinoic acid / positive regulation of cardiac muscle cell proliferation / FRS-mediated FGFR2 signaling / positive regulation of vascular associated smooth muscle cell proliferation / cellular response to transforming growth factor beta stimulus / Signaling by FGFR2 in disease / epithelial cell differentiation / axonogenesis / regulation of ERK1 and ERK2 cascade / post-embryonic development / positive regulation of epithelial cell proliferation / Negative regulation of FGFR2 signaling / animal organ morphogenesis / lung development / bone development / receptor protein-tyrosine kinase / peptidyl-tyrosine phosphorylation / Constitutive Signaling by Aberrant PI3K in Cancer Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Valverde, R. / Foster, L. | ||||||
Funding support | 1items
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![]() | ![]() Title: Discovery of lirafugratinib (RLY-4008), a highly selective irreversible small-molecule inhibitor of FGFR2. Authors: Schonherr, H. / Ayaz, P. / Taylor, A.M. / Casaletto, J.B. / Toure, B.B. / Moustakas, D.T. / Hudson, B.M. / Valverde, R. / Zhao, S. / O'Hearn, P.J. / Foster, L. / Sharon, D.A. / Garfinkle, S. ...Authors: Schonherr, H. / Ayaz, P. / Taylor, A.M. / Casaletto, J.B. / Toure, B.B. / Moustakas, D.T. / Hudson, B.M. / Valverde, R. / Zhao, S. / O'Hearn, P.J. / Foster, L. / Sharon, D.A. / Garfinkle, S. / Giordanetto, F. / Lescarbeau, A. / Kurukulasuriya, R. / Gerami-Moayed, N. / Maglic, D. / Bruderek, K. / Naik, G. / Gunaydin, H. / Mader, M.M. / Boezio, A.A. / McLean, T.H. / Chen, R. / Wang, Y. / Shaw, D.E. / Watters, J. / Bergstrom, D.A. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 252.6 KB | Display | ![]() |
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PDB format | ![]() | 188.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.3 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 25.2 KB | Display | |
Data in CIF | ![]() | 34 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8u1fC ![]() 3ri1S S: Starting model for refinement C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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2 | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 36121.621 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: P21802, receptor protein-tyrosine kinase #2: Chemical | ChemComp-GOL / #3: Chemical | ChemComp-GSH / | #4: Chemical | Mass: 399.445 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C23H21N5O2 / Feature type: SUBJECT OF INVESTIGATION #5: Water | ChemComp-HOH / | Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.77 Å3/Da / Density % sol: 55.64 % |
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Crystal grow | Temperature: 291.15 K / Method: vapor diffusion, hanging drop / pH: 7.5 Details: 27 % PEG 4000, 0.1 M Hepes pH7.5, 0.252 M Ammonium Sulfate, 0.05 M GSH GSSG PH range: 7-8 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS PILATUS3 S 6M / Detector: PIXEL / Date: Aug 29, 2018 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.11584 Å / Relative weight: 1 |
Reflection | Resolution: 2.23→78.37 Å / Num. obs: 38979 / % possible obs: 99.94 % / Redundancy: 6.7 % / Biso Wilson estimate: 37.85 Å2 / CC1/2: 0.995 / Net I/σ(I): 5.3 |
Reflection shell | Resolution: 2.23→2.34 Å / Mean I/σ(I) obs: 1.25 / Num. unique obs: 7553 / CC1/2: 0.75 / % possible all: 99.9 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 3RI1 Resolution: 2.24→78.37 Å / SU ML: 0.3321 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 28.337 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 46.73 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.24→78.37 Å
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Refine LS restraints |
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LS refinement shell |
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