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Yorodumi- PDB-5kh9: Crystal structure of a low occupancy fragment candidate (5-[(4-Is... -
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-Basic information
Entry | Database: PDB / ID: 5kh9 | ||||||
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Title | Crystal structure of a low occupancy fragment candidate (5-[(4-Isopropylphenyl)amino]-6-methyl-1,2,4-triazin-3(2H)-one) bound in the ubiquitin binding pocket of the HDAC6 zinc-finger domain | ||||||
Components | Histone deacetylase 6HDAC6 | ||||||
Keywords | HYDROLASE / HISTONE DEACETYLASE / HDAC / HDAC6 / FRAGMENT SCREENING / STRUCTURAL GENOMICS CONSORTIUM / SGC / DIAMOND I04-1 XCHEM / PANDDA | ||||||
Function / homology | Function and homology information negative regulation of hydrogen peroxide metabolic process / cellular response to topologically incorrect protein / polyubiquitinated misfolded protein transport / positive regulation of cellular response to oxidative stress / erythrocyte enucleation / positive regulation of cholangiocyte proliferation / response to misfolded protein / negative regulation of oxidoreductase activity / regulation of microtubule-based movement / parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization ...negative regulation of hydrogen peroxide metabolic process / cellular response to topologically incorrect protein / polyubiquitinated misfolded protein transport / positive regulation of cellular response to oxidative stress / erythrocyte enucleation / positive regulation of cholangiocyte proliferation / response to misfolded protein / negative regulation of oxidoreductase activity / regulation of microtubule-based movement / parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization / negative regulation of protein-containing complex disassembly / protein-containing complex disassembly / negative regulation of axon extension involved in axon guidance / tubulin deacetylation / regulation of establishment of protein localization / positive regulation of tubulin deacetylation / Cilium Assembly / peptidyl-lysine deacetylation / collateral sprouting / tubulin deacetylase activity / regulation of autophagy of mitochondrion / Transcriptional regulation by RUNX2 / lysosome localization / negative regulation of microtubule depolymerization / negative regulation of protein acetylation / misfolded protein binding / ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway / protein deacetylation / cilium disassembly / response to growth factor / dendritic spine morphogenesis / aggresome assembly / histone deacetylase / regulation of androgen receptor signaling pathway / cellular response to misfolded protein / protein lysine deacetylase activity / positive regulation of signaling receptor activity / aggresome / cellular response to parathyroid hormone stimulus / positive regulation of dendrite morphogenesis / microtubule associated complex / Hydrolases; Acting on carbon-nitrogen bonds, other than peptide bonds; In linear amides / regulation of fat cell differentiation / histone deacetylase activity / negative regulation of gene expression, epigenetic / dynein complex binding / response to corticosterone / protein quality control for misfolded or incompletely synthesized proteins / beta-tubulin binding / axonal transport of mitochondrion / response to dexamethasone / positive regulation of epithelial cell migration / Notch-HLH transcription pathway / cell leading edge / RUNX2 regulates osteoblast differentiation / alpha-tubulin binding / histone deacetylase complex / polyubiquitin modification-dependent protein binding / cilium assembly / response to immobilization stress / HSF1 activation / regulation of macroautophagy / negative regulation of protein-containing complex assembly / inclusion body / axon cytoplasm / response to amphetamine / multivesicular body / positive regulation of synaptic transmission, glutamatergic / transcription corepressor binding / ciliary basal body / ubiquitin binding / regulation of autophagy / actin filament organization / caveola / negative regulation of proteolysis / intracellular protein transport / Hsp90 protein binding / Late endosomal microautophagy / tau protein binding / protein destabilization / regulation of protein stability / NOTCH1 Intracellular Domain Regulates Transcription / cellular response to hydrogen peroxide / beta-catenin binding / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / autophagy / Aggrephagy / Chaperone Mediated Autophagy / protein polyubiquitination / histone deacetylase binding / cellular response to heat / positive regulation of peptidyl-serine phosphorylation / actin binding / perikaryon / microtubule binding / microtubule / RNA polymerase II cis-regulatory region sequence-specific DNA binding / axon / centrosome Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / Resolution: 1.07 Å | ||||||
Authors | Harding, R.J. / Tempel, W. / Ravichandran, M. / Collins, P. / Pearce, N. / Brandao-Neto, J. / Douangamath, A. / Schapira, M. / Bountra, C. / Edwards, A.M. ...Harding, R.J. / Tempel, W. / Ravichandran, M. / Collins, P. / Pearce, N. / Brandao-Neto, J. / Douangamath, A. / Schapira, M. / Bountra, C. / Edwards, A.M. / von Delft, F. / Santhakumar, V. / Arrowsmith, C.M. / Structural Genomics Consortium (SGC) | ||||||
Citation | Journal: J. Med. Chem. / Year: 2017 Title: Small Molecule Antagonists of the Interaction between the Histone Deacetylase 6 Zinc-Finger Domain and Ubiquitin. Authors: Harding, R.J. / Ferreira de Freitas, R. / Collins, P. / Franzoni, I. / Ravichandran, M. / Ouyang, H. / Juarez-Ornelas, K.A. / Lautens, M. / Schapira, M. / von Delft, F. / Santhakumar, V. / Arrowsmith, C.H. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5kh9.cif.gz | 65.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5kh9.ent.gz | 45.6 KB | Display | PDB format |
PDBx/mmJSON format | 5kh9.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/kh/5kh9 ftp://data.pdbj.org/pub/pdb/validation_reports/kh/5kh9 | HTTPS FTP |
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-Related structure data
Related structure data | 5b8dC 5kh3C 5kh7C 5wpbC 3c5kS 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
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 11932.607 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HDAC6, KIAA0901, JM21 / Plasmid: pET28-lic / Production host: Escherichia coli (E. coli) / Strain (production host): BL21 (DE3) codon plus / References: UniProt: Q9UBN7, histone deacetylase |
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-Non-polymers , 6 types, 118 molecules
#2: Chemical | #3: Chemical | ChemComp-FMT / | #4: Chemical | ChemComp-6T5 / | #5: Chemical | ChemComp-UNX / #6: Chemical | ChemComp-NA / | #7: 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: 2.17 Å3/Da / Density % sol: 43.26 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, sitting drop / pH: 4.6 Details: 2M Na-formate, 0.2M Na-acetate pH4.6, 5% ethylene glycol |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I04-1 / Wavelength: 0.92819 Å | ||||||||||||||||||
Detector | Type: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Oct 2, 2015 | ||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||
Radiation wavelength | Wavelength: 0.92819 Å / Relative weight: 1 | ||||||||||||||||||
Reflection | Resolution: 1.07→34.81 Å / Num. obs: 46238 / % possible obs: 99.4 % / Redundancy: 5.5 % / CC1/2: 0.999 / Rmerge(I) obs: 0.062 / Rpim(I) all: 0.028 / Rrim(I) all: 0.069 / Net I/σ(I): 13.5 / Num. measured all: 256160 | ||||||||||||||||||
Reflection shell |
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-Processing
Software |
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Refinement | Starting model: pdbid 3C5K Resolution: 1.07→34.8 Å / Cor.coef. Fo:Fc: 0.979 / Cor.coef. Fo:Fc free: 0.978 / SU B: 0.931 / SU ML: 0.02 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.025 / ESU R Free: 0.024 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: Users of this crystal structure: verify our intepretion of the electron density. Amplitudes and unmerged intensities are included with this deposition. Diffraction images will be deposited ...Details: Users of this crystal structure: verify our intepretion of the electron density. Amplitudes and unmerged intensities are included with this deposition. Diffraction images will be deposited in a public repository. Geometry restraints for the fragment candidate were prepared with GRADE. Ambiguous difference density suggests some form of covalent modification of Cys1147.
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 193.07 Å2 / Biso mean: 14.755 Å2 / Biso min: 7.96 Å2
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Refinement step | Cycle: final / Resolution: 1.07→34.8 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.07→1.098 Å / Total num. of bins used: 20
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