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- PDB-6sis: Crystal structure of macrocyclic PROTAC 1 in complex with the sec... -
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Open data
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Basic information
Entry | Database: PDB / ID: 6sis | ||||||
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Title | Crystal structure of macrocyclic PROTAC 1 in complex with the second bromodomain of human Brd4 and pVHL:ElonginC:ElonginB | ||||||
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![]() | LIGASE / PROTAC COMPLEX / MACROCYCLE / TARGETED DEGRADATION | ||||||
Function / homology | ![]() regulation of cellular response to hypoxia / RHOBTB3 ATPase cycle / negative regulation of receptor signaling pathway via JAK-STAT / transcription elongation factor activity / target-directed miRNA degradation / elongin complex / VCB complex / Replication of the SARS-CoV-1 genome / Cul5-RING ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex ...regulation of cellular response to hypoxia / RHOBTB3 ATPase cycle / negative regulation of receptor signaling pathway via JAK-STAT / transcription elongation factor activity / target-directed miRNA degradation / elongin complex / VCB complex / Replication of the SARS-CoV-1 genome / Cul5-RING ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / intracellular non-membrane-bounded organelle / SUMOylation of ubiquitinylation proteins / negative regulation of transcription elongation by RNA polymerase II / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / RNA polymerase II C-terminal domain binding / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / negative regulation of DNA damage checkpoint / P-TEFb complex binding / ubiquitin-like ligase-substrate adaptor activity / negative regulation by host of viral transcription / Tat-mediated elongation of the HIV-1 transcript / Formation of HIV-1 elongation complex containing HIV-1 Tat / Formation of HIV elongation complex in the absence of HIV Tat / negative regulation of signal transduction / RNA Polymerase II Transcription Elongation / positive regulation of T-helper 17 cell lineage commitment / Formation of RNA Pol II elongation complex / negative regulation of TORC1 signaling / RNA Polymerase II Pre-transcription Events / positive regulation of G2/M transition of mitotic cell cycle / histone reader activity / RNA polymerase II CTD heptapeptide repeat kinase activity / negative regulation of autophagy / transcription corepressor binding / condensed nuclear chromosome / transcription initiation at RNA polymerase II promoter / TP53 Regulates Transcription of DNA Repair Genes / positive regulation of cell differentiation / positive regulation of transcription elongation by RNA polymerase II / transcription elongation by RNA polymerase II / transcription coregulator activity / Vif-mediated degradation of APOBEC3G / lysine-acetylated histone binding / cell morphogenesis / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Inactivation of CSF3 (G-CSF) signaling / Evasion by RSV of host interferon responses / Regulation of expression of SLITs and ROBOs / ubiquitin-protein transferase activity / transcription corepressor activity / p53 binding / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Antigen processing: Ubiquitination & Proteasome degradation / chromosome / Neddylation / protein-macromolecule adaptor activity / Replication of the SARS-CoV-2 genome / regulation of inflammatory response / cellular response to hypoxia / ubiquitin-dependent protein catabolic process / regulation of gene expression / protein-containing complex assembly / proteasome-mediated ubiquitin-dependent protein catabolic process / DNA-binding transcription factor binding / positive regulation of canonical NF-kappaB signal transduction / amyloid fibril formation / Potential therapeutics for SARS / molecular adaptor activity / transcription coactivator activity / protein stabilization / transcription cis-regulatory region binding / protein ubiquitination / chromatin remodeling / negative regulation of cell population proliferation / negative regulation of gene expression / ubiquitin protein ligase binding / DNA damage response / chromatin binding / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / negative regulation of apoptotic process / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / enzyme binding / endoplasmic reticulum / positive regulation of transcription by RNA polymerase II / mitochondrion / proteolysis / nucleoplasm / nucleus / plasma membrane / cytosol Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Hughes, S.J. / Testa, A. / Ciulli, A. | ||||||
![]() | ![]() Title: Structure-Based Design of a Macrocyclic PROTAC. Authors: Testa, A. / Hughes, S.J. / Lucas, X. / Wright, J.E. / Ciulli, A. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 377.3 KB | Display | ![]() |
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PDB format | ![]() | 313.3 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 5t35S S: Starting model for refinement |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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1 | ![]()
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Component-ID: _ / Refine code: _
NCS ensembles :
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Components
-Protein , 4 types, 8 molecules AEBFCGDH
#1: Protein | Mass: 15060.332 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Protein | Mass: 11748.406 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #3: Protein | Mass: 10974.616 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #4: Protein | Mass: 18702.291 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Non-polymers , 2 types, 9 molecules ![](data/chem/img/LFE.gif)
![](data/chem/img/HOH.gif)
![](data/chem/img/HOH.gif)
#5: Chemical | #6: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 3.75 Å3/Da / Density % sol: 67.22 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7.5 Details: 10% (w/v) PEG 8000, 0.1 M Tris-HCl (pH 7.5) and 0.1 M MgCl2 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | |||||||||||||||||||||||||||
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Diffraction source | Source: ![]() ![]() ![]() | |||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Mar 10, 2018 | |||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.975 Å / Relative weight: 1 | |||||||||||||||||||||||||||
Reflection | Resolution: 3.5→49.73 Å / Num. obs: 19211 / % possible obs: 92.6 % / Redundancy: 2.6 % / CC1/2: 0.984 / Rmerge(I) obs: 0.16 / Rpim(I) all: 0.109 / Rrim(I) all: 0.194 / Net I/σ(I): 4.5 | |||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1 / Redundancy: 2.6 %
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 5T35 Resolution: 3.5→49.73 Å / Cor.coef. Fo:Fc: 0.919 / Cor.coef. Fo:Fc free: 0.906 / SU B: 87.198 / SU ML: 0.56 / SU R Cruickshank DPI: 0.5358 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.573 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: 1.1 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 184.64 Å2 / Biso mean: 105.444 Å2 / Biso min: 28.22 Å2
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Refinement step | Cycle: final / Resolution: 3.5→49.73 Å
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Refine LS restraints |
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Refine LS restraints NCS | Refine-ID: X-RAY DIFFRACTION / Type: interatomic distance / Weight position: 0.05
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LS refinement shell | Resolution: 3.5→3.913 Å / Rfactor Rfree error: 0 / Total num. of bins used: 5
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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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