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Yorodumi- PDB-2brn: Structure-based Design of Novel Chk1 Inhibitors: Insights into Hy... -
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-Basic information
Entry | Database: PDB / ID: 2brn | ||||||
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Title | Structure-based Design of Novel Chk1 Inhibitors: Insights into Hydrogen Bonding and Protein-Ligand Affinity | ||||||
Components | SERINE/THREONINE-PROTEIN KINASE CHK1 | ||||||
Keywords | TRANSFERASE / DRUG DESIGN / FURANOPYRIMIDINE / MOLECULAR RECOGNITION / ONCOLOGY / PYRROLOPYRIMIDINE / ATP-BINDING / CELL CYCLE / DNA DAMAGE / KINASE / NUCLEAR PROTEIN / PHOSPHORYLATION / POLYMORPHISM / SERINE/THREONINE-PROTEIN KINASE | ||||||
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 / negative regulation of mitotic nuclear division / mitotic G2/M transition checkpoint / regulation of mitotic centrosome separation / nucleus organization / inner cell mass cell proliferation / 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 / negative regulation of mitotic nuclear division / mitotic G2/M transition checkpoint / regulation of mitotic centrosome separation / nucleus organization / inner cell mass cell proliferation / negative regulation of gene expression, epigenetic / regulation of double-strand break repair via homologous recombination / 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 / Activation of ATR in response to replication stress / positive regulation of cell cycle / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / signal transduction in response to DNA damage / replication fork / DNA damage checkpoint signaling / condensed nuclear chromosome / regulation of signal transduction by p53 class mediator / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / TP53 Regulates Transcription of DNA Repair Genes / peptidyl-threonine phosphorylation / G2/M DNA damage checkpoint / Signaling by SCF-KIT / cellular response to mechanical stimulus / G2/M transition of mitotic cell cycle / regulation of cell population proliferation / Processing of DNA double-strand break ends / Regulation of TP53 Activity through Phosphorylation / DNA replication / non-specific serine/threonine protein kinase / protein kinase activity / intracellular signal transduction / chromatin remodeling / protein domain specific binding / protein phosphorylation / DNA repair / protein serine kinase activity / intracellular membrane-bounded organelle / protein serine/threonine kinase activity / centrosome / apoptotic process / DNA damage response / chromatin / 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: 2.8 Å | ||||||
Authors | Foloppe, N. / Fisher, L.M. / Howes, R. / Kierstan, P. / Potter, A. / Robertson, A.G.S. / Surgenor, A.E. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2005 Title: Structure-Based Design of Novel Chk1 Inhibitors: Insights Into Hydrogen Bonding and Protein-Ligand Affinity. Authors: Foloppe, N. / Fisher, L.M. / Howes, R. / Kierstan, P. / Potter, A. / Robertson, A.G.S. / Surgenor, A.E. | ||||||
History |
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Remark 700 | SHEET THE SHEET STRUCTURE OF THIS MOLECULE IS BIFURCATED. IN ORDER TO REPRESENT THIS FEATURE IN ... SHEET THE SHEET STRUCTURE OF THIS MOLECULE IS BIFURCATED. IN ORDER TO REPRESENT THIS FEATURE IN THE SHEET RECORDS BELOW, TWO SHEETS ARE DEFINED. |
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 2brn.cif.gz | 71.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb2brn.ent.gz | 51.8 KB | Display | PDB format |
PDBx/mmJSON format | 2brn.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/br/2brn ftp://data.pdbj.org/pub/pdb/validation_reports/br/2brn | HTTPS FTP |
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-Related structure data
Related structure data | 2br1C 2brbC 2brgC 2brhC 2brmC 2broC 1ia8S S: Starting model for refinement C: citing same article (ref.) |
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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: 34148.148 Da / Num. of mol.: 1 / Fragment: N-TERMINAL KINASE DOMAIN, RESIDUES 1-289 Source method: isolated from a genetically manipulated source Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PFASTBAC1/CHK1 1-289 C8H / Cell line (production host): SF9 / Production host: SPODOPTERA FRUGIPERDA (fall armyworm) / References: UniProt: O14757, EC: 2.7.1.37 |
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#2: Chemical | ChemComp-DF1 / ( |
#3: Water | ChemComp-HOH / |
Compound details | FUNCTION: PARTICIPATES IN THE ARREST OF THE CELL CYCLE WHEN THE DNA IS DAMAGED OR WHEN UNLIGATED ...FUNCTION: PARTICIPAT |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.9 Å3/Da / Density % sol: 56.9 % |
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Crystal grow | pH: 7.5 / Details: pH 7.50 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: ID29 / Wavelength: 0.9792 |
Detector | Type: MARRESEARCH / Detector: CCD |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9792 Å / Relative weight: 1 |
Reflection | Resolution: 2.8→30 Å / Num. obs: 7714 / % possible obs: 97.9 % / Observed criterion σ(I): 2 / Redundancy: 3.2 % / Rmerge(I) obs: 0.13 / Net I/σ(I): 9.1 |
Reflection shell | Resolution: 2.8→2.9 Å / Redundancy: 3.2 % / Rmerge(I) obs: 0.51 / Mean I/σ(I) obs: 1 / % possible all: 98.9 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 1IA8 Resolution: 2.8→65.94 Å / Cor.coef. Fo:Fc: 0.921 / Cor.coef. Fo:Fc free: 0.85 / SU B: 16.281 / SU ML: 0.327 / Cross valid method: THROUGHOUT / ESU R Free: 0.464 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS.
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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: BABINET MODEL WITH MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 45.58 Å2
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Refinement step | Cycle: LAST / Resolution: 2.8→65.94 Å
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