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Yorodumi- PDB-7s4e: Crystal Structure of ligand ACBi1 in complex with bromodomain of ... -
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-Basic information
Entry | Database: PDB / ID: 7s4e | ||||||
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Title | Crystal Structure of ligand ACBi1 in complex with bromodomain of human Smarca2 and pVHL:ElonginC:ElonginB complex | ||||||
Components |
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Keywords | GENE REGULATION / Complex / PROTAC / Degradation / Assembly | ||||||
Function / homology | Function and homology information regulation of cellular response to hypoxia / RHOBTB3 ATPase cycle / negative regulation of receptor signaling pathway via JAK-STAT / target-directed miRNA degradation / transcription elongation factor activity / 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 / target-directed miRNA degradation / transcription elongation factor activity / elongin complex / VCB complex / Replication of the SARS-CoV-1 genome / Cul5-RING ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / intracellular membraneless 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 / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / Tat-mediated elongation of the HIV-1 transcript / ubiquitin-like ligase-substrate adaptor activity / 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 / Formation of RNA Pol II elongation complex / negative regulation of TORC1 signaling / RNA Polymerase II Pre-transcription Events / negative regulation of autophagy / transcription corepressor binding / TP53 Regulates Transcription of DNA Repair Genes / transcription initiation at RNA polymerase II promoter / positive regulation of cell differentiation / transcription elongation by RNA polymerase II / Vif-mediated degradation of APOBEC3G / Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement / cell morphogenesis / Inactivation of CSF3 (G-CSF) signaling / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Evasion by RSV of host interferon responses / Regulation of expression of SLITs and ROBOs / ubiquitin-protein transferase activity / transcription corepressor activity / Antigen processing: Ubiquitination & Proteasome degradation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Neddylation / Replication of the SARS-CoV-2 genome / protein-macromolecule adaptor activity / cellular response to hypoxia / ubiquitin-dependent protein catabolic process / regulation of gene expression / protein-containing complex assembly / DNA-binding transcription factor binding / proteasome-mediated ubiquitin-dependent protein catabolic process / amyloid fibril formation / molecular adaptor activity / protein stabilization / protein ubiquitination / negative regulation of cell population proliferation / negative regulation of gene expression / ubiquitin protein ligase 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 / mitochondrion / proteolysis / nucleoplasm / nucleus / plasma membrane / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.25 Å | ||||||
Authors | MacPherson, D.J. / Sherman, W. | ||||||
Funding support | United States, 1items
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Citation | Journal: Nat Commun / Year: 2022 Title: Predicting the structural basis of targeted protein degradation by integrating molecular dynamics simulations with structural mass spectrometry. Authors: Dixon, T. / MacPherson, D. / Mostofian, B. / Dauzhenka, T. / Lotz, S. / McGee, D. / Shechter, S. / Shrestha, U.R. / Wiewiora, R. / McDargh, Z.A. / Pei, F. / Pal, R. / Ribeiro, J.V. / ...Authors: Dixon, T. / MacPherson, D. / Mostofian, B. / Dauzhenka, T. / Lotz, S. / McGee, D. / Shechter, S. / Shrestha, U.R. / Wiewiora, R. / McDargh, Z.A. / Pei, F. / Pal, R. / Ribeiro, J.V. / Wilkerson, T. / Sachdeva, V. / Gao, N. / Jain, S. / Sparks, S. / Li, Y. / Vinitsky, A. / Zhang, X. / Razavi, A.M. / Kolossvary, I. / Imbriglio, J. / Evdokimov, A. / Bergeron, L. / Zhou, W. / Adhikari, J. / Ruprecht, B. / Dickson, A. / Xu, H. / Sherman, W. / Izaguirre, J.A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7s4e.cif.gz | 393.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7s4e.ent.gz | 320.2 KB | Display | PDB format |
PDBx/mmJSON format | 7s4e.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7s4e_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 7s4e_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 7s4e_validation.xml.gz | 35.4 KB | Display | |
Data in CIF | 7s4e_validation.cif.gz | 48.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/s4/7s4e ftp://data.pdbj.org/pub/pdb/validation_reports/s4/7s4e | HTTPS FTP |
-Related structure data
Related structure data | 6haxS S: Starting model for refinement |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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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: 14420.502 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SMARCA2, BAF190B, BRM, SNF2A, SNF2L2 / Production host: Escherichia coli BL21(DE3) (bacteria) References: UniProt: P51531-2, Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement #2: Protein | Mass: 18702.291 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: VHL / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P40337 #3: Protein | Mass: 10843.420 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ELOC, TCEB1 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q15369 #4: Protein | Mass: 11748.406 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ELOB, TCEB2 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q15370 |
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-Non-polymers , 5 types, 109 molecules
#5: Chemical | ChemComp-EDO / #6: Chemical | ChemComp-NA / #7: Chemical | #8: Chemical | #9: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | Y |
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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: 2.68 Å3/Da / Density % sol: 54.05 % |
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Crystal grow | Temperature: 277.15 K / Method: vapor diffusion, hanging drop / pH: 7.85 Details: 0.1 M HEPES, pH 7.85, 13% PEG 3350, 0.2 M sodium formate PH range: 7.85 |
-Data collection
Diffraction | Mean temperature: 77.15 K / Serial crystal experiment: N | ||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: NSLS-II / Beamline: 17-ID-2 / Wavelength: 0.97932 Å | ||||||||||||||||||||||||||||||
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jun 5, 2021 | ||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.97932 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||
Reflection | Resolution: 2.25→37.92 Å / Num. obs: 55100 / % possible obs: 99.9 % / Redundancy: 7.4 % / CC1/2: 0.998 / Rmerge(I) obs: 0.149 / Rpim(I) all: 0.058 / Rrim(I) all: 0.16 / Net I/σ(I): 8 | ||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6HAX Resolution: 2.25→37.92 Å / Cor.coef. Fo:Fc: 0.957 / Cor.coef. Fo:Fc free: 0.937 / SU B: 21.882 / SU ML: 0.244 / Cross valid method: FREE R-VALUE / σ(F): 0 / ESU R: 0.296 / ESU R Free: 0.226 / Stereochemistry target values: MAXIMUM LIKELIHOOD 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 / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 138.83 Å2 / Biso mean: 61.139 Å2 / Biso min: 31.42 Å2
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Refinement step | Cycle: final / Resolution: 2.25→37.92 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: 2.25→2.308 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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