+Open data
-Basic information
Entry | Database: PDB / ID: 6odb | ||||||
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Title | Crystal structure of HDAC8 in complex with compound 3 | ||||||
Components | Histone deacetylase 8 | ||||||
Keywords | HYDROLASE / histone deacetylase / HDAC8 / hydroxamic acid | ||||||
Function / homology | Function and homology information histone decrotonylase activity / histone deacetylase / protein lysine deacetylase activity / regulation of telomere maintenance / Hydrolases; Acting on carbon-nitrogen bonds, other than peptide bonds; In linear amides / mitotic sister chromatid cohesion / histone deacetylase activity / nuclear chromosome / Notch-HLH transcription pathway / histone deacetylase complex ...histone decrotonylase activity / histone deacetylase / protein lysine deacetylase activity / regulation of telomere maintenance / Hydrolases; Acting on carbon-nitrogen bonds, other than peptide bonds; In linear amides / mitotic sister chromatid cohesion / histone deacetylase activity / nuclear chromosome / Notch-HLH transcription pathway / histone deacetylase complex / negative regulation of protein ubiquitination / Resolution of Sister Chromatid Cohesion / Hsp70 protein binding / HDACs deacetylate histones / Hsp90 protein binding / regulation of protein stability / NOTCH1 Intracellular Domain Regulates Transcription / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / Separation of Sister Chromatids / chromatin organization / DNA-binding transcription factor binding / negative regulation of transcription by RNA polymerase II / nucleoplasm / metal ion binding / nucleus / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.7 Å | ||||||
Authors | Zheng, X. / Conti, C. / Caravella, J. / Zablocki, M.-M. / Bair, K. / Barczak, N. / Han, B. / Lancia Jr., D. / Liu, C. / Martin, M. ...Zheng, X. / Conti, C. / Caravella, J. / Zablocki, M.-M. / Bair, K. / Barczak, N. / Han, B. / Lancia Jr., D. / Liu, C. / Martin, M. / Ng, P.Y. / Rudnitskaya, A. / Thomason, J.J. / Garcia-Dancey, R. / Hardy, C. / Lahdenranta, J. / Leng, C. / Li, P. / Pardo, E. / Saldahna, A. / Tan, T. / Toms, A.V. / Yao, L. / Zhang, C. | ||||||
Citation | Journal: To Be Published Title: Structure-based Discovery of Novel N-(E)-N-Hydroxy-3-(2-(2-oxoimidazolidin-1-yl)phenyl)acrylamides as Potent and Selective HDAC8 inhibitors Authors: Zheng, X. / Conti, C. / Caravella, J. / Zablocki, M.-M. / Bair, K. / Barczak, N. / Han, B. / Lancia Jr., D. / Liu, C. / Martin, M. / Ng, P.Y. / Rudnitskaya, A. / Thomason, J.J. / Garcia- ...Authors: Zheng, X. / Conti, C. / Caravella, J. / Zablocki, M.-M. / Bair, K. / Barczak, N. / Han, B. / Lancia Jr., D. / Liu, C. / Martin, M. / Ng, P.Y. / Rudnitskaya, A. / Thomason, J.J. / Garcia-Dancey, R. / Hardy, C. / Lahdenranta, J. / Leng, C. / Li, P. / Pardo, E. / Saldahna, A. / Tan, T. / Toms, A.V. / Yao, L. / Zhang, C. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6odb.cif.gz | 229.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6odb.ent.gz | 181.5 KB | Display | PDB format |
PDBx/mmJSON format | 6odb.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/od/6odb ftp://data.pdbj.org/pub/pdb/validation_reports/od/6odb | HTTPS FTP |
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-Related structure data
Related structure data | 6odaC 6odcC 1t64S 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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2 |
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3 |
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Component-ID: 0 / Beg auth comp-ID: LEU / Beg label comp-ID: LEU / End auth comp-ID: VAL / End label comp-ID: VAL / Refine code: 0 / Auth seq-ID: 14 - 376 / Label seq-ID: 38 - 400
NCS ensembles :
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-Components
-Protein , 1 types, 3 molecules ABC
#1: Protein | Mass: 45975.906 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HDAC8, HDACL1, CDA07 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: Q9BY41, histone deacetylase |
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-Non-polymers , 5 types, 106 molecules
#2: Chemical | #3: Chemical | #4: Chemical | ChemComp-K / #5: Chemical | ChemComp-GOL / #6: 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: 2.69 Å3/Da / Density % sol: 54.29 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop / pH: 5.3 Details: 0.1M MES pH5.3, 5% PEG6000, 0.12M Gly-Gly-Gly, 2mM TCEP |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SSRF / Beamline: BL17U / Wavelength: 0.99 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Dec 15, 2014 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.99 Å / Relative weight: 1 |
Reflection | Resolution: 2.7→50 Å / Num. obs: 38256 / % possible obs: 99.8 % / Redundancy: 3.7 % / Rmerge(I) obs: 0.098 / Net I/σ(I): 13.6 |
Reflection shell | Resolution: 2.7→2.8 Å / Redundancy: 3.7 % / Rmerge(I) obs: 0.617 / Mean I/σ(I) obs: 2.3 / Num. unique obs: 2838 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1t64 Resolution: 2.7→50 Å / Cor.coef. Fo:Fc: 0.944 / Cor.coef. Fo:Fc free: 0.913 / SU B: 12.404 / SU ML: 0.244 / Cross valid method: THROUGHOUT / ESU R: 0.825 / ESU R Free: 0.315 / 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: 1.2 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 55.017 Å2
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Refinement step | Cycle: 1 / Resolution: 2.7→50 Å
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Refine LS restraints |
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