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Yorodumi- PDB-4agw: Discovery of a small molecule type II inhibitor of wild-type and ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4agw | ||||||
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Title | Discovery of a small molecule type II inhibitor of wild-type and gatekeeper mutants of BCR-ABL, PDGFRalpha, Kit, and Src kinases | ||||||
Components | PROTO-ONCOGENE TYROSINE-PROTEIN KINASE SRC | ||||||
Keywords | TRANSFERASE / ATP-BINDING / LIPOPROTEIN / MYRISTATE / PHOSPHOPROTEIN / SH2 DOMAIN / SH3 DOMAIN | ||||||
Function / homology | Function and homology information Signaling by ERBB2 / Nuclear signaling by ERBB4 / PIP3 activates AKT signaling / Signaling by SCF-KIT / Regulation of KIT signaling / Signaling by EGFR / GAB1 signalosome / Regulation of gap junction activity / FCGR activation / PECAM1 interactions ...Signaling by ERBB2 / Nuclear signaling by ERBB4 / PIP3 activates AKT signaling / Signaling by SCF-KIT / Regulation of KIT signaling / Signaling by EGFR / GAB1 signalosome / Regulation of gap junction activity / FCGR activation / PECAM1 interactions / CD28 co-stimulation / CTLA4 inhibitory signaling / EPHA-mediated growth cone collapse / Ephrin signaling / G alpha (i) signalling events / GP1b-IX-V activation signalling / Recycling pathway of L1 / Thrombin signalling through proteinase activated receptors (PARs) / VEGFR2 mediated cell proliferation / RAF activation / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / RET signaling / Receptor Mediated Mitophagy / ADP signalling through P2Y purinoceptor 1 / Downregulation of ERBB4 signaling / EPH-ephrin mediated repulsion of cells / Cyclin D associated events in G1 / Regulation of RUNX3 expression and activity / Activated NTRK3 signals through PI3K / Downstream signal transduction / MAP2K and MAPK activation / Integrin signaling / GRB2:SOS provides linkage to MAPK signaling for Integrins / MET activates PTK2 signaling / Extra-nuclear estrogen signaling / EPHB-mediated forward signaling / p130Cas linkage to MAPK signaling for integrins / VEGFA-VEGFR2 Pathway / connexin binding / osteoclast development / progesterone receptor signaling pathway / negative regulation of intrinsic apoptotic signaling pathway / bone resorption / extrinsic component of cytoplasmic side of plasma membrane / negative regulation of extrinsic apoptotic signaling pathway / non-specific protein-tyrosine kinase / non-membrane spanning protein tyrosine kinase activity / epidermal growth factor receptor signaling pathway / cell junction / protein phosphatase binding / protein tyrosine kinase activity / mitochondrial inner membrane / cell differentiation / cytoskeleton / endosome membrane / regulation of cell cycle / cell adhesion / cell cycle / phosphorylation / signaling receptor binding / focal adhesion / innate immune response / heme binding / perinuclear region of cytoplasm / protein-containing complex / ATP binding / membrane / nucleus / plasma membrane / cytosol Similarity search - Function | ||||||
Biological species | GALLUS GALLUS (chicken) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / OTHER / Resolution: 2.6 Å | ||||||
Authors | Weisberg, E. / Choi, H.G. / Seeliger, M. / Gray, N. / Griffin, J.D. | ||||||
Citation | Journal: Blood / Year: 2010 Title: Discovery of a Small-Molecule Type II Inhibitor of Wild-Type and Gatekeeper Mutants of Bcr-Abl, Pdgfralpha, Kit, and Src Kinases: Novel Type II Inhibitor of Gatekeeper Mutants. Authors: Weisberg, E. / Choi, H.G. / Ray, A. / Barrett, R. / Zhang, J. / Sim, T. / Zhou, W. / Seeliger, M. / Cameron, M. / Azam, M. / Fletcher, J.A. / Debiec-Rychter, M. / Mayeda, M. / Moreno, D. / ...Authors: Weisberg, E. / Choi, H.G. / Ray, A. / Barrett, R. / Zhang, J. / Sim, T. / Zhou, W. / Seeliger, M. / Cameron, M. / Azam, M. / Fletcher, J.A. / Debiec-Rychter, M. / Mayeda, M. / Moreno, D. / Kung, A.L. / Janne, P.A. / Khosravi-Far, R. / Melo, J.V. / Manley, P.W. / Adamia, S. / Wu, C. / Gray, N. / Griffin, J.D. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4agw.cif.gz | 119.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4agw.ent.gz | 97.8 KB | Display | PDB format |
PDBx/mmJSON format | 4agw.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ag/4agw ftp://data.pdbj.org/pub/pdb/validation_reports/ag/4agw | HTTPS FTP |
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-Related structure data
Related structure data | |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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2 |
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments:
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-Components
#1: Protein | Mass: 32726.645 Da / Num. of mol.: 2 / Fragment: KINASE DOMAIN, RESIDUES 251-533 Source method: isolated from a genetically manipulated source Source: (gene. exp.) GALLUS GALLUS (chicken) / Production host: ESCHERICHIA COLI (E. coli) References: UniProt: P00523, non-specific protein-tyrosine kinase #2: Chemical | #3: Chemical | #4: Chemical | ChemComp-GOL / | #5: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.7 Å3/Da / Density % sol: 54.42 % / Description: NONE |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop Details: PROTEIN CONCENTRATION 0.3 MM INHIBITOR CONCENTRATION 0.5 MM METHOD HANGING DROP VAPOR DIFFUSION AT 298 K PROTEIN BUFFER 5 % DMSO, 20 MM TRIS PH 8.0, 250 MM NACL, 5 % GLYCEROL, 1 MM DTT. ...Details: PROTEIN CONCENTRATION 0.3 MM INHIBITOR CONCENTRATION 0.5 MM METHOD HANGING DROP VAPOR DIFFUSION AT 298 K PROTEIN BUFFER 5 % DMSO, 20 MM TRIS PH 8.0, 250 MM NACL, 5 % GLYCEROL, 1 MM DTT. MOTHER LIQUOR: 100 MM MES PH 6.5, 7.5 % PEG 3350, 10 % GLYCEROL, 1 MM DTT |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 8.2.1 / Wavelength: 1 |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Apr 24, 2009 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.5→50 Å / Num. obs: 19430 / % possible obs: 93.4 % / Observed criterion σ(I): 0 / Rmerge(I) obs: 0.11 / Net I/σ(I): 7.2 |
-Processing
Software |
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Refinement | Method to determine structure: OTHER Starting model: NONE Resolution: 2.6→42.267 Å / SU ML: 0.42 / σ(F): 0.1 / Phase error: 29.29 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 30.258 Å2 / ksol: 0.331 e/Å3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters |
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Refinement step | Cycle: LAST / Resolution: 2.6→42.267 Å
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Refine LS restraints |
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Refine LS restraints NCS |
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LS refinement shell |
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