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Yorodumi- PDB-5ops: Structure of CHK1 10-pt. mutant complex with pyrrolopyridine LRRK... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5ops | ||||||
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Title | Structure of CHK1 10-pt. mutant complex with pyrrolopyridine LRRK2 inhibitor | ||||||
Components | Serine/threonine-protein kinase Chk1 | ||||||
Keywords | TRANSFERASE / Parkinson's disease / Leucine-rich repeat kinase 2 / LRRK2 / Checkpoint kinase 1 / CHK1 / mutant / surrogate / kinase inhibitor | ||||||
Function / homology | Function and homology information negative regulation of G0 to G1 transition / apoptotic process involved in development / histone H3T11 kinase activity / negative regulation of DNA biosynthetic process / mitotic G2/M transition checkpoint / negative regulation of mitotic nuclear division / regulation of mitotic centrosome separation / inner cell mass cell proliferation / regulation of double-strand break repair via homologous recombination / negative regulation of gene expression, epigenetic ...negative regulation of G0 to G1 transition / apoptotic process involved in development / histone H3T11 kinase activity / negative regulation of DNA biosynthetic process / mitotic G2/M transition checkpoint / negative regulation of mitotic nuclear division / regulation of mitotic centrosome separation / inner cell mass cell proliferation / regulation of double-strand break repair via homologous recombination / negative regulation of gene expression, epigenetic / nucleus organization / cellular response to caffeine / Transcriptional Regulation by E2F6 / mitotic G2 DNA damage checkpoint signaling / Presynaptic phase of homologous DNA pairing and strand exchange / replicative senescence / signal transduction in response to DNA damage / Activation of ATR in response to replication stress / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / positive regulation of cell cycle / condensed nuclear chromosome / regulation of signal transduction by p53 class mediator / DNA damage checkpoint signaling / replication fork / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / TP53 Regulates Transcription of DNA Repair Genes / peptidyl-threonine phosphorylation / Signaling by SCF-KIT / G2/M DNA damage checkpoint / cellular response to mechanical stimulus / G2/M transition of mitotic cell cycle / regulation of cell population proliferation / Processing of DNA double-strand break ends / DNA replication / Regulation of TP53 Activity through Phosphorylation / non-specific serine/threonine protein kinase / protein kinase activity / chromatin remodeling / protein domain specific binding / protein phosphorylation / intracellular membrane-bounded organelle / DNA repair / protein serine kinase activity / protein serine/threonine kinase activity / centrosome / DNA damage response / chromatin / apoptotic process / protein-containing complex / extracellular space / nucleoplasm / ATP binding / nucleus / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2 Å | ||||||
Authors | Dokurno, P. / Williamson, D.S. / Acheson-Dossang, P. / Chen, I. / Murray, J.B. / Shaw, T. / Surgenor, A.E. | ||||||
Citation | Journal: J. Med. Chem. / Year: 2017 Title: Design of Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors Using a Crystallographic Surrogate Derived from Checkpoint Kinase 1 (CHK1). Authors: Williamson, D.S. / Smith, G.P. / Acheson-Dossang, P. / Bedford, S.T. / Chell, V. / Chen, I.J. / Daechsel, J.C.A. / Daniels, Z. / David, L. / Dokurno, P. / Hentzer, M. / Herzig, M.C. / ...Authors: Williamson, D.S. / Smith, G.P. / Acheson-Dossang, P. / Bedford, S.T. / Chell, V. / Chen, I.J. / Daechsel, J.C.A. / Daniels, Z. / David, L. / Dokurno, P. / Hentzer, M. / Herzig, M.C. / Hubbard, R.E. / Moore, J.D. / Murray, J.B. / Newland, S. / Ray, S.C. / Shaw, T. / Surgenor, A.E. / Terry, L. / Thirstrup, K. / Wang, Y. / Christensen, K.V. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5ops.cif.gz | 71.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5ops.ent.gz | 50.6 KB | Display | PDB format |
PDBx/mmJSON format | 5ops.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/op/5ops ftp://data.pdbj.org/pub/pdb/validation_reports/op/5ops | HTTPS FTP |
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-Related structure data
Related structure data | 5oopC 5oorC 5ootC 5op2C 5op4C 5op5C 5op7C 5opbC 5oprC 5opuC 5opvC 5oq5C 5oq6C 5oq7C 5oq8C 1nvrS C: citing same article (ref.) 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: 34094.207 Da / Num. of mol.: 1 Mutation: N59L, V68I, L84M, Y86L, C87A, E91S, E134H, S147A, F149Y, G150S Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CHEK1, CHK1 / Plasmid: Pfastbac1 / Cell line (production host): SF9 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: O14757, non-specific serine/threonine protein kinase |
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#2: Chemical | ChemComp-A3Q / |
#3: 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: 2.31 Å3/Da / Density % sol: 46.73 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.5 Details: 7% PEG 8000, 0.1 M MES buffer pH 6.5, 20% ethylene glycol |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Apr 1, 2012 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.979→44.174 Å / Num. all: 21501 / Num. obs: 21501 / % possible obs: 99 % / Redundancy: 2.8 % / Rpim(I) all: 0.033 / Rrim(I) all: 0.058 / Rsym value: 0.04 / Net I/av σ(I): 12 / Net I/σ(I): 13.3 / Num. measured all: 60633 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1NVR Resolution: 2→40 Å / Cor.coef. Fo:Fc: 0.97 / Cor.coef. Fo:Fc free: 0.949 / SU B: 3.717 / SU ML: 0.102 / SU R Cruickshank DPI: 0.1478 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.148 / ESU R Free: 0.138 Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 143.05 Å2 / Biso mean: 39.547 Å2 / Biso min: 17.41 Å2
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Refinement step | Cycle: final / Resolution: 2→40 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2→2.108 Å / Rfactor Rfree error: 0 / Total num. of bins used: 10
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