+Open data
-Basic information
Entry | Database: PDB / ID: 6rl6 | ||||||
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Title | Fragment AZ-024 binding at the p53pT387/14-3-3 sigma interface | ||||||
Components |
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Keywords | PEPTIDE BINDING PROTEIN / protein protein interaction / fragment soaking / stabilization | ||||||
Function / homology | Function and homology information Loss of function of TP53 in cancer due to loss of tetramerization ability / Regulation of TP53 Expression / signal transduction by p53 class mediator / negative regulation of G1 to G0 transition / negative regulation of glucose catabolic process to lactate via pyruvate / Transcriptional activation of cell cycle inhibitor p21 / regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Activation of NOXA and translocation to mitochondria / negative regulation of pentose-phosphate shunt / ATP-dependent DNA/DNA annealing activity ...Loss of function of TP53 in cancer due to loss of tetramerization ability / Regulation of TP53 Expression / signal transduction by p53 class mediator / negative regulation of G1 to G0 transition / negative regulation of glucose catabolic process to lactate via pyruvate / Transcriptional activation of cell cycle inhibitor p21 / regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Activation of NOXA and translocation to mitochondria / negative regulation of pentose-phosphate shunt / ATP-dependent DNA/DNA annealing activity / negative regulation of helicase activity / regulation of cell cycle G2/M phase transition / intrinsic apoptotic signaling pathway in response to hypoxia / regulation of fibroblast apoptotic process / oxidative stress-induced premature senescence / oligodendrocyte apoptotic process / negative regulation of miRNA processing / positive regulation of thymocyte apoptotic process / glucose catabolic process to lactate via pyruvate / regulation of tissue remodeling / positive regulation of mitochondrial membrane permeability / negative regulation of mitophagy / positive regulation of programmed necrotic cell death / mRNA transcription / bone marrow development / circadian behavior / histone deacetylase regulator activity / germ cell nucleus / regulation of mitochondrial membrane permeability involved in apoptotic process / RUNX3 regulates CDKN1A transcription / regulation of DNA damage response, signal transduction by p53 class mediator / TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain / TP53 Regulates Transcription of Death Receptors and Ligands / Activation of PUMA and translocation to mitochondria / DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / negative regulation of glial cell proliferation / negative regulation of neuroblast proliferation / Regulation of TP53 Activity through Association with Co-factors / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / mitochondrial DNA repair / T cell lineage commitment / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / ER overload response / regulation of epidermal cell division / protein kinase C inhibitor activity / negative regulation of DNA replication / B cell lineage commitment / positive regulation of cardiac muscle cell apoptotic process / thymocyte apoptotic process / positive regulation of epidermal cell differentiation / TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain / keratinocyte development / keratinization / TP53 Regulates Transcription of Caspase Activators and Caspases / mitotic G1 DNA damage checkpoint signaling / cardiac septum morphogenesis / positive regulation of execution phase of apoptosis / entrainment of circadian clock by photoperiod / PI5P Regulates TP53 Acetylation / Association of TriC/CCT with target proteins during biosynthesis / Zygotic genome activation (ZGA) / necroptotic process / positive regulation of release of cytochrome c from mitochondria / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / rRNA transcription / TFIID-class transcription factor complex binding / negative regulation of telomere maintenance via telomerase / SUMOylation of transcription factors / Regulation of localization of FOXO transcription factors / intrinsic apoptotic signaling pathway by p53 class mediator / general transcription initiation factor binding / keratinocyte proliferation / mitophagy / Transcriptional Regulation by VENTX / DNA damage response, signal transduction by p53 class mediator / response to X-ray / phosphoserine residue binding / replicative senescence / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / cellular response to UV-C / neuroblast proliferation / : / Activation of BAD and translocation to mitochondria / negative regulation of reactive oxygen species metabolic process / hematopoietic stem cell differentiation / chromosome organization / positive regulation of RNA polymerase II transcription preinitiation complex assembly / negative regulation of keratinocyte proliferation / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / T cell proliferation involved in immune response / glial cell proliferation / establishment of skin barrier / Pyroptosis / cis-regulatory region sequence-specific DNA binding / embryonic organ development / SARS-CoV-2 targets host intracellular signalling and regulatory pathways / hematopoietic progenitor cell differentiation / cellular response to actinomycin D / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / somitogenesis Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.6 Å | ||||||
Authors | Genet, S. / Wolter, M. / Guillory, X. / Somsen, B. / Leysen, S. / Patel, J. / 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 | 6rl6.cif.gz | 115.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6rl6.ent.gz | 87.9 KB | Display | PDB format |
PDBx/mmJSON format | 6rl6.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6rl6_validation.pdf.gz | 724.4 KB | Display | wwPDB validaton report |
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Full document | 6rl6_full_validation.pdf.gz | 726.5 KB | Display | |
Data in XML | 6rl6_validation.xml.gz | 15.1 KB | Display | |
Data in CIF | 6rl6_validation.cif.gz | 22.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/rl/6rl6 ftp://data.pdbj.org/pub/pdb/validation_reports/rl/6rl6 | HTTPS FTP |
-Related structure data
Related structure data | 6r5lC 6rhcC 6rjlC 6rjqC 6rjzC 6rk8C 6rkiC 6rkkC 6rkmC 6rl3C 6rl4C 6rm5C 6rm7C 6rp6C 6rwhC 6rwiC 6rwsC 6rwuC 6rx2C 6s39C 6s3cC 6s40C 6s9qC 6sinC 6sioC 6sipC 6siqC 6slvC 6slwC 6slxC 5mocS 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
-Protein / Protein/peptide , 2 types, 2 molecules AP
#1: Protein | Mass: 28226.518 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: Residues -4 to 0 are expression tag / 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: 1449.520 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P04637 |
-Non-polymers , 4 types, 319 molecules
#3: Chemical | ChemComp-MG / |
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#4: Chemical | ChemComp-CL / |
#5: Chemical | ChemComp-K7Q / ~{ |
#6: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.43 Å3/Da / Density % sol: 49.32 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7.5 Details: 0.1M Hepes, pH7.5, 27%PEG, 5% Glycerol, 0.2M Calcium Chloride, 2mM DTT. |
-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: 1.0332 Å |
Detector | Type: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: May 18, 2018 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.0332 Å / Relative weight: 1 |
Reflection | Resolution: 1.6→62.57 Å / Num. obs: 38480 / % possible obs: 100 % / Redundancy: 12.7 % / CC1/2: 1 / Rrim(I) all: 0.049 / Net I/σ(I): 32.8 |
Reflection shell | Resolution: 1.6→1.63 Å / Redundancy: 12.9 % / Mean I/σ(I) obs: 10.1 / Num. unique obs: 1889 / CC1/2: 0.988 / Rrim(I) all: 0.22 / % possible all: 99.2 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5MOC Resolution: 1.6→45.484 Å / SU ML: 0.11 / Cross valid method: FREE R-VALUE / σ(F): 1.53 / Phase error: 16.47
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.6→45.484 Å
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Refine LS restraints |
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LS refinement shell |
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