[English] 日本語
Yorodumi- PDB-5ipj: Crystal structure of human Pim-1 kinase in complex with a quinazo... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5ipj | ||||||
---|---|---|---|---|---|---|---|
Title | Crystal structure of human Pim-1 kinase in complex with a quinazolinone-pyrrolopyrrolone inhibitor. | ||||||
Components | Serine/threonine-protein kinase pim-1 | ||||||
Keywords | transferase/transferase inhibitor / TRANSFERASE / serine/threonine protein kinase / transferase-transferase inhibitor complex | ||||||
Function / homology | Function and homology information positive regulation of cardioblast proliferation / cellular detoxification / regulation of hematopoietic stem cell proliferation / vitamin D receptor signaling pathway / 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 / positive regulation of TORC1 signaling ...positive regulation of cardioblast proliferation / cellular detoxification / regulation of hematopoietic stem cell proliferation / vitamin D receptor signaling pathway / 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 / positive regulation of TORC1 signaling / Signaling by FLT3 fusion proteins / negative regulation of innate immune response / positive regulation of brown fat cell differentiation / 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 / protein stabilization / non-specific serine/threonine protein kinase / cell cycle / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / apoptotic process / nucleolus / negative regulation of 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 / MOLECULAR REPLACEMENT / Resolution: 2.1 Å | ||||||
Authors | Mohr, C. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2016 Title: Discovery and Optimization of Quinazolinone-pyrrolopyrrolones as Potent and Orally Bioavailable Pan-Pim Kinase Inhibitors. Authors: Pettus, L.H. / Andrews, K.L. / Booker, S.K. / Chen, J. / Cee, V.J. / Chavez, F. / Chen, Y. / Eastwood, H. / Guerrero, N. / Herberich, B. / Hickman, D. / Lanman, B.A. / Laszlo, J. / Lee, M.R. ...Authors: Pettus, L.H. / Andrews, K.L. / Booker, S.K. / Chen, J. / Cee, V.J. / Chavez, F. / Chen, Y. / Eastwood, H. / Guerrero, N. / Herberich, B. / Hickman, D. / Lanman, B.A. / Laszlo, J. / Lee, M.R. / Lipford, J.R. / Mattson, B. / Mohr, C. / Nguyen, Y. / Norman, M.H. / Powers, D. / Reed, A.B. / Rex, K. / Sastri, C. / Tamayo, N. / Wang, P. / Winston, J.T. / Wu, B. / Wu, T. / Wurz, R.P. / Xu, Y. / Zhou, Y. / Tasker, A.S. / Wang, H.L. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 5ipj.cif.gz | 75.3 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb5ipj.ent.gz | 54.4 KB | Display | PDB format |
PDBx/mmJSON format | 5ipj.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ip/5ipj ftp://data.pdbj.org/pub/pdb/validation_reports/ip/5ipj | HTTPS FTP |
---|
-Related structure data
Similar structure data |
---|
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-Components
#1: Protein | Mass: 33064.422 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PIM1 / Production host: Escherichia coli (E. coli) References: UniProt: P11309, non-specific serine/threonine protein kinase | ||
---|---|---|---|
#2: Chemical | ChemComp-6CD / | ||
#3: Chemical | #4: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 3.34 Å3/Da / Density % sol: 63.19 % |
---|---|
Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 8 / Details: 1.0M LiCl, 0.1M TRIS pH8.0, 20% PEG6K |
-Data collection
Diffraction | Mean temperature: 100 K |
---|---|
Diffraction source | Source: ROTATING ANODE / Type: RIGAKU FR-E SUPERBRIGHT / Wavelength: 1.5418 Å |
Detector | Type: RIGAKU SATURN 92 / Detector: CCD / Date: Oct 4, 2012 / Details: VariMax HF |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 2.1→30 Å / Num. obs: 25440 / % possible obs: 98.2 % / Redundancy: 4.2 % / Rmerge(I) obs: 0.079 / Net I/σ(I): 12.9 |
Reflection shell | Resolution: 2.1→2.18 Å / Redundancy: 4.1 % / Rmerge(I) obs: 0.44 / Mean I/σ(I) obs: 3.3 / % possible all: 97.3 |
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.1→28.12 Å / Cor.coef. Fo:Fc: 0.961 / Cor.coef. Fo:Fc free: 0.944 / SU B: 4.138 / SU ML: 0.106 / Cross valid method: THROUGHOUT / ESU R: 0.161 / ESU R Free: 0.152 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 42.691 Å2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: 1 / Resolution: 2.1→28.12 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
|