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Yorodumi- PDB-3umw: Crystal structure of Pim1 kinase in complex with inhibitor (Z)-2-... -
+Open data
-Basic information
Entry | Database: PDB / ID: 3umw | ||||||
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Title | Crystal structure of Pim1 kinase in complex with inhibitor (Z)-2-[(1H-indazol-3-yl)methylene]-6-methoxy-7-(piperazin-1-ylmethyl)benzofuran-3(2H)-one | ||||||
Components | Proto-oncogene serine/threonine-protein kinase pim-1 | ||||||
Keywords | TRANSFERASE/INHIBITOR / PIM1 / kinase inhibitor / rational drug design / leukemia / TRANSFERASE-INHIBITOR complex | ||||||
Function / homology | Function and homology information positive regulation of cardioblast proliferation / regulation of hematopoietic stem cell proliferation / vitamin D receptor signaling pathway / cellular detoxification / STAT5 activation downstream of FLT3 ITD mutants / transcription factor binding / ribosomal small subunit binding / positive regulation of cyclin-dependent protein serine/threonine kinase activity / positive regulation of cardiac muscle cell proliferation / negative regulation of innate immune response ...positive regulation of cardioblast proliferation / regulation of hematopoietic stem cell proliferation / vitamin D receptor signaling pathway / cellular detoxification / STAT5 activation downstream of FLT3 ITD mutants / transcription factor binding / ribosomal small subunit binding / positive regulation of cyclin-dependent protein serine/threonine kinase activity / positive regulation of cardiac muscle cell proliferation / negative regulation of innate immune response / Signaling by FLT3 fusion proteins / positive regulation of brown fat cell differentiation / positive regulation of TORC1 signaling / protein serine/threonine kinase activator activity / regulation of transmembrane transporter activity / positive regulation of protein serine/threonine kinase activity / negative regulation of DNA-binding transcription factor activity / cellular response to type II interferon / manganese ion binding / Interleukin-4 and Interleukin-13 signaling / protein autophosphorylation / non-specific serine/threonine protein kinase / protein stabilization / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / negative regulation of apoptotic process / nucleolus / apoptotic process / positive regulation of DNA-templated transcription / nucleoplasm / ATP binding / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.08 Å | ||||||
Authors | Parker, L.J. / Handa, N. / Yokoyama, S. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2012 Title: Rational evolution of a novel type of potent and selective proviral integration site in Moloney murine leukemia virus kinase 1 (PIM1) inhibitor from a screening-hit compound. Authors: Nakano, H. / Saito, N. / Parker, L.J. / Tada, Y. / Abe, M. / Tsuganezawa, K. / Yokoyama, S. / Tanaka, A. / Kojima, H. / Okabe, T. / Nagano, T. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3umw.cif.gz | 77.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3umw.ent.gz | 54.9 KB | Display | PDB format |
PDBx/mmJSON format | 3umw.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 3umw_validation.pdf.gz | 841.1 KB | Display | wwPDB validaton report |
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Full document | 3umw_full_validation.pdf.gz | 843.6 KB | Display | |
Data in XML | 3umw_validation.xml.gz | 14.7 KB | Display | |
Data in CIF | 3umw_validation.cif.gz | 21.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/um/3umw ftp://data.pdbj.org/pub/pdb/validation_reports/um/3umw | HTTPS FTP |
-Related structure data
Related structure data | 3a99S S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 34187.727 Da / Num. of mol.: 1 / Fragment: KINASE DOMAIN (UNP RESIDUES 120-404) Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: pim1 / Plasmid: pCR2.1-TOPO / Production host: cell-free protein synthesis (unknown) References: UniProt: P11309, non-specific serine/threonine protein kinase |
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#2: Chemical | ChemComp-GOL / |
#3: Chemical | ChemComp-SO4 / |
#4: Chemical | ChemComp-596 / ( |
#5: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.29 Å3/Da / Density % sol: 62.6 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 5.5 Details: 100mM Citrate buffer pH 5.5, 200mM NaCl, 1M NH4HPO4, vapor diffusion, hanging drop, temperature 293K |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: SPring-8 / Beamline: BL26B2 / Wavelength: 1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: RAYONIX MX-225 / Detector: CCD / Date: Jan 24, 2011 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Monochromator: Fixed exit Si double crystal monochromator / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.08→32.174 Å / Num. all: 26602 / Num. obs: 26602 / % possible obs: 99.7 % / Redundancy: 6.4 % / Biso Wilson estimate: 29.1 Å2 / Rmerge(I) obs: 0.078 / Rsym value: 0.078 / Net I/σ(I): 6 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3A99 Resolution: 2.08→32.17 Å / Cor.coef. Fo:Fc: 0.958 / Cor.coef. Fo:Fc free: 0.945 / WRfactor Rfree: 0.2053 / WRfactor Rwork: 0.1765 / Occupancy max: 1 / Occupancy min: 0.5 / FOM work R set: 0.8882 / SU B: 3.111 / SU ML: 0.085 / SU R Cruickshank DPI: 0.1453 / SU Rfree: 0.1316 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.132 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 63.95 Å2 / Biso mean: 30.2034 Å2 / Biso min: 5.97 Å2
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Refinement step | Cycle: LAST / Resolution: 2.08→32.17 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.08→2.134 Å / Total num. of bins used: 20
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