+Open data
-Basic information
Entry | Database: PDB / ID: 6rhc | ||||||
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Title | Fragment AZ-003 binding at the TAZpS89/14-3-3 sigma interface | ||||||
Components |
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Keywords | PEPTIDE BINDING PROTEIN / protein protein interaction / fragment soaking / stabilization | ||||||
Function / homology | Function and homology information kidney morphogenesis / regulation of metanephric nephron tubule epithelial cell differentiation / Physiological factors / RUNX3 regulates YAP1-mediated transcription / mesenchymal cell differentiation / YAP1- and WWTR1 (TAZ)-stimulated gene expression / heart process / stem cell division / hippo signaling / tissue homeostasis ...kidney morphogenesis / regulation of metanephric nephron tubule epithelial cell differentiation / Physiological factors / RUNX3 regulates YAP1-mediated transcription / mesenchymal cell differentiation / YAP1- and WWTR1 (TAZ)-stimulated gene expression / heart process / stem cell division / hippo signaling / tissue homeostasis / EGR2 and SOX10-mediated initiation of Schwann cell myelination / SMAD protein signal transduction / glomerulus development / Signaling by Hippo / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / negative regulation of fat cell differentiation / regulation of epidermal cell division / protein kinase C inhibitor activity / positive regulation of epidermal cell differentiation / keratinocyte development / keratinization / RUNX2 regulates osteoblast differentiation / Regulation of localization of FOXO transcription factors / keratinocyte proliferation / phosphoserine residue binding / cilium assembly / Activation of BAD and translocation to mitochondria / negative regulation of keratinocyte proliferation / establishment of skin barrier / SARS-CoV-2 targets host intracellular signalling and regulatory pathways / positive regulation of osteoblast differentiation / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / positive regulation of epithelial to mesenchymal transition / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / negative regulation of stem cell proliferation / RHO GTPases activate PKNs / protein kinase A signaling / protein sequestering activity / negative regulation of innate immune response / protein export from nucleus / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / positive regulation of protein export from nucleus / release of cytochrome c from mitochondria / negative regulation of protein phosphorylation / stem cell proliferation / Translocation of SLC2A4 (GLUT4) to the plasma membrane / TP53 Regulates Metabolic Genes / Downregulation of SMAD2/3:SMAD4 transcriptional activity / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / negative regulation of protein kinase activity / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / negative regulation of canonical Wnt signaling pathway / multicellular organism growth / positive regulation of protein localization to nucleus / osteoblast differentiation / transcription corepressor activity / intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of cell growth / transcription regulator complex / transcription coactivator activity / nuclear body / regulation of cell cycle / protein ubiquitination / cadherin binding / positive regulation of cell population proliferation / regulation of DNA-templated transcription / protein kinase binding / negative regulation of transcription by RNA polymerase II / signal transduction / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / extracellular space / extracellular exosome / nucleoplasm / identical protein binding / nucleus / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.2 Å | ||||||
Authors | Genet, S. / Wolter, M. / Guillory, X. / Somsen, B. / Leysen, S. / Castaldi, P. / Ottmann, C. | ||||||
Funding support | Netherlands, 1items
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Citation | Journal: J.Med.Chem. / Year: 2020 Title: Fragment-based Differential Targeting of PPI Stabilizer Interfaces. Authors: Guillory, X. / Wolter, M. / Leysen, S. / Neves, J.F. / Kuusk, A. / Genet, S. / Somsen, B. / Morrow, J.K. / Rivers, E. / van Beek, L. / Patel, J. / Goodnow, R. / Schoenherr, H. / Fuller, N. / ...Authors: Guillory, X. / Wolter, M. / Leysen, S. / Neves, J.F. / Kuusk, A. / Genet, S. / Somsen, B. / Morrow, J.K. / Rivers, E. / van Beek, L. / Patel, J. / Goodnow, R. / Schoenherr, H. / Fuller, N. / Cao, Q. / Doveston, R.G. / Brunsveld, L. / Arkin, M.R. / Castaldi, P. / Boyd, H. / Landrieu, I. / Chen, H. / Ottmann, C. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6rhc.cif.gz | 73.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6rhc.ent.gz | 51.6 KB | Display | PDB format |
PDBx/mmJSON format | 6rhc.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6rhc_validation.pdf.gz | 739.4 KB | Display | wwPDB validaton report |
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Full document | 6rhc_full_validation.pdf.gz | 739.6 KB | Display | |
Data in XML | 6rhc_validation.xml.gz | 14.2 KB | Display | |
Data in CIF | 6rhc_validation.cif.gz | 21.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/rh/6rhc ftp://data.pdbj.org/pub/pdb/validation_reports/rh/6rhc | HTTPS FTP |
-Related structure data
Related structure data | 6r5lC 6rjlC 6rjqC 6rjzC 6rk8C 6rkiC 6rkkC 6rkmC 6rl3C 6rl4C 6rl6C 6rm5C 6rm7C 6rp6C 6rwhC 6rwiC 6rwsC 6rwuC 6rx2C 6s39C 6s3cC 6s40C 6s9qC 6sinC 6sioC 6sipC 6siqC 6slvC 6slwC 6slxC 3mhrS 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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1 |
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Unit cell |
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Components on special symmetry positions |
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-Components
-Protein / Protein/peptide , 2 types, 2 molecules AP
#1: Protein | Mass: 26542.914 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SFN, HME1 / Production host: Escherichia coli (E. coli) / References: UniProt: P31947 |
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#2: Protein/peptide | Mass: 1422.439 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: Q9GZV5 |
-Non-polymers , 4 types, 300 molecules
#3: Chemical | #4: Chemical | #5: Chemical | ChemComp-K48 / | #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: 2.67 Å3/Da / Density % sol: 53.99 % |
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Crystal grow | Temperature: 277.15 K / Method: vapor diffusion, hanging drop / pH: 7.5 Details: Protein and peptide were mixed at a 1:2 molar stoichiometry with a final protein concentration of 12 mg/mL in crystallization buffer. This was used during hanging-drop crystallization in a 1: ...Details: Protein and peptide were mixed at a 1:2 molar stoichiometry with a final protein concentration of 12 mg/mL in crystallization buffer. This was used during hanging-drop crystallization in a 1:1 ratio with 0.1 M HEPES pH 7.5, 0.2 M CaCl2, 5% glycerol, 2 mM BME and 28% PEG400. Crystals were grown within 10 days at 4 C and fragment soaking was performed on crystals of 10 days and older by adding 0.2 uL of a 100 mM stock solution in dimethyl sulfoxide to 2 uL drops containing multiple crystals. |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: PETRA III, DESY / Beamline: P11 / Wavelength: 1.033191 Å |
Detector | Type: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Oct 28, 2018 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.033191 Å / Relative weight: 1 |
Reflection | Resolution: 1.2→41.83 Å / Num. obs: 89802 / % possible obs: 99.3 % / Redundancy: 12.8 % / CC1/2: 0.997 / Rrim(I) all: 0.113 / Net I/σ(I): 11.3 |
Reflection shell | Resolution: 1.2→1.22 Å / Redundancy: 12.8 % / Mean I/σ(I) obs: 2.1 / Num. unique obs: 4345 / CC1/2: 0.575 / Rrim(I) all: 0.937 / % possible all: 97.3 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3MHR Resolution: 1.2→41.83 Å / Cor.coef. Fo:Fc: 0.97 / Cor.coef. Fo:Fc free: 0.967 / SU B: 0.684 / SU ML: 0.029 / Cross valid method: THROUGHOUT / ESU R: 0.038 / ESU R Free: 0.039 / 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: 14.636 Å2
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Refinement step | Cycle: LAST / Resolution: 1.2→41.83 Å
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Refine LS restraints |
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