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- PDB-6g0s: Crystal Structure of the first bromodomain of human BRD4 in compl... -
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Open data
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Basic information
Entry | Database: PDB / ID: 6g0s | ||||||
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Title | Crystal Structure of the first bromodomain of human BRD4 in complex with an acetylated SIRT7 peptide (K272ac/K275ac) | ||||||
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![]() | TRANSCRIPTION / Bromodomain / complex | ||||||
Function / homology | ![]() : / regulation of transcription of nucleolar large rRNA by RNA polymerase I / : / nucleolus organizer region / : / : / : / protein depropionylation / protein-propionyllysine depropionylase activity / protein deglutarylation ...: / regulation of transcription of nucleolar large rRNA by RNA polymerase I / : / nucleolus organizer region / : / : / : / protein depropionylation / protein-propionyllysine depropionylase activity / protein deglutarylation / peptidyl-lysine desuccinylation / protein-glutaryllysine deglutarylase activity / NAD-dependent histone H3K18 deacetylase activity / regulation of double-strand break repair via nonhomologous end joining / protein-succinyllysine desuccinylase activity / deacetylase activity / R-loop processing / homologous chromosome pairing at meiosis / NAD-dependent protein lysine deacetylase activity / positive regulation of rRNA processing / protein acetyllysine N-acetyltransferase / protein deacetylation / regulation of protein export from nucleus / regulation of mitochondrion organization / regulation of gluconeogenesis / histone deacetylase activity / rRNA transcription / RNA polymerase II C-terminal domain binding / negative regulation of DNA damage checkpoint / P-TEFb complex binding / NAD+ binding / negative regulation by host of viral transcription / regulation of DNA repair / positive regulation of T-helper 17 cell lineage commitment / negative regulation of protein ubiquitination / Transferases; Acyltransferases; Transferring groups other than aminoacyl groups / positive regulation of G2/M transition of mitotic cell cycle / histone reader activity / RNA polymerase II CTD heptapeptide repeat kinase activity / condensed nuclear chromosome / positive regulation of transcription elongation by RNA polymerase II / transcription coregulator activity / lysine-acetylated histone binding / osteoblast differentiation / transcription corepressor activity / p53 binding / chromosome / site of double-strand break / regulation of inflammatory response / positive regulation of canonical NF-kappaB signal transduction / Potential therapeutics for SARS / transcription coactivator activity / transcription cis-regulatory region binding / chromatin remodeling / DNA repair / DNA damage response / chromatin binding / chromatin / regulation of transcription by RNA polymerase II / nucleolus / positive regulation of DNA-templated transcription / enzyme binding / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / nucleoplasm / nucleus / metal ion binding / cytoplasm Similarity search - Function | ||||||
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Method | ![]() ![]() ![]() ![]() | ||||||
![]() | Filippakopoulos, P. / Picaud, S. / Krojer, T. / von Delft, F. / Arrowsmith, C.H. / Edwards, A.M. / Bountra, C. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Interactome Rewiring Following Pharmacological Targeting of BET Bromodomains. Authors: Jean-Philippe Lambert / Sarah Picaud / Takao Fujisawa / Huayun Hou / Pavel Savitsky / Liis Uusküla-Reimand / Gagan D Gupta / Hala Abdouni / Zhen-Yuan Lin / Monika Tucholska / James D R ...Authors: Jean-Philippe Lambert / Sarah Picaud / Takao Fujisawa / Huayun Hou / Pavel Savitsky / Liis Uusküla-Reimand / Gagan D Gupta / Hala Abdouni / Zhen-Yuan Lin / Monika Tucholska / James D R Knight / Beatriz Gonzalez-Badillo / Nicole St-Denis / Joseph A Newman / Manuel Stucki / Laurence Pelletier / Nuno Bandeira / Michael D Wilson / Panagis Filippakopoulos / Anne-Claude Gingras / ![]() ![]() ![]() ![]() ![]() Abstract: Targeting bromodomains (BRDs) of the bromo-and-extra-terminal (BET) family offers opportunities for therapeutic intervention in cancer and other diseases. Here, we profile the interactomes of BRD2, ...Targeting bromodomains (BRDs) of the bromo-and-extra-terminal (BET) family offers opportunities for therapeutic intervention in cancer and other diseases. Here, we profile the interactomes of BRD2, BRD3, BRD4, and BRDT following treatment with the pan-BET BRD inhibitor JQ1, revealing broad rewiring of the interaction landscape, with three distinct classes of behavior for the 603 unique interactors identified. A group of proteins associate in a JQ1-sensitive manner with BET BRDs through canonical and new binding modes, while two classes of extra-terminal (ET)-domain binding motifs mediate acetylation-independent interactions. Last, we identify an unexpected increase in several interactions following JQ1 treatment that define negative functions for BRD3 in the regulation of rRNA synthesis and potentially RNAPII-dependent gene expression that result in decreased cell proliferation. Together, our data highlight the contributions of BET protein modules to their interactomes allowing for a better understanding of pharmacological rewiring in response to JQ1. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 124.5 KB | Display | ![]() |
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PDB format | ![]() | 95.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 5nncC ![]() 5nndC ![]() 5nneC ![]() 5nnfC ![]() 5nngC ![]() 6g0oC ![]() 6g0pC ![]() 6g0qC ![]() 6g0rC ![]() 2grcS ![]() 2oo1S ![]() 2ossS ![]() 2ouoS ![]() 3d7cS ![]() 3daiS ![]() 3dwyS S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 15099.380 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Protein/peptide | | Mass: 1410.677 Da / Num. of mol.: 1 / Source method: obtained synthetically Details: SIRT7 peptide acetylated at K272 and K275 C-terminal TYR added for UV detection Source: (synth.) ![]() References: UniProt: Q9NRC8, Hydrolases; Acting on carbon-nitrogen bonds, other than peptide bonds; In linear amides #3: Chemical | #4: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.12 Å3/Da / Density % sol: 41.88 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 8.5 Details: 20.0 % PEG3350 10.0 % EtGly 0.1 M bis-tris-propane pH 8.5 0.2M NaOOCCH3 |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: ![]() ![]() ![]() | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Apr 28, 2016 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9763 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.475→51.805 Å / Num. all: 45984 / Num. obs: 45984 / % possible obs: 100 % / Redundancy: 7.2 % / Rpim(I) all: 0.031 / Rrim(I) all: 0.084 / Rsym value: 0.077 / Net I/av σ(I): 7.4 / Net I/σ(I): 14.5 / Num. measured all: 328804 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Phasing
Phasing | Method: ![]() | |||||||||
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Phasing MR | Model details: Phaser MODE: MR_AUTO
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Processing
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Refinement | Method to determine structure: ![]() Starting model: Ensemble of 2OSS, 2OUO, 2GRC, 2OO1, 3DAI, 3D7C, 3DWY Resolution: 1.48→51.8 Å / Cor.coef. Fo:Fc: 0.966 / Cor.coef. Fo:Fc free: 0.956 / SU B: 2.795 / SU ML: 0.052 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.071 / ESU R Free: 0.074 Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
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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: 65.9 Å2 / Biso mean: 21.015 Å2 / Biso min: 9.82 Å2
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Refinement step | Cycle: final / Resolution: 1.48→51.8 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.475→1.513 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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