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- PDB-9ngt: Crystal structure of CRBN-DDB1 and FPFT-2216 in complex with mTOR -
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Open data
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Basic information
Entry | Database: PDB / ID: 9ngt | ||||||
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Title | Crystal structure of CRBN-DDB1 and FPFT-2216 in complex with mTOR | ||||||
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![]() | DNA Binding Protein/Transferase / Ternary complex / Molecular glue degrader / neosubstrate / DNA Binding Protein-Transferase complex | ||||||
Function / homology | ![]() RNA polymerase III type 2 promoter sequence-specific DNA binding / RNA polymerase III type 1 promoter sequence-specific DNA binding / positive regulation of cytoplasmic translational initiation / regulation of locomotor rhythm / T-helper 1 cell lineage commitment / positive regulation of pentose-phosphate shunt / positive regulation of wound healing, spreading of epidermal cells / TORC2 signaling / negative regulation of monoatomic ion transmembrane transport / TORC2 complex ...RNA polymerase III type 2 promoter sequence-specific DNA binding / RNA polymerase III type 1 promoter sequence-specific DNA binding / positive regulation of cytoplasmic translational initiation / regulation of locomotor rhythm / T-helper 1 cell lineage commitment / positive regulation of pentose-phosphate shunt / positive regulation of wound healing, spreading of epidermal cells / TORC2 signaling / negative regulation of monoatomic ion transmembrane transport / TORC2 complex / regulation of membrane permeability / cellular response to leucine starvation / negative regulation of lysosome organization / heart valve morphogenesis / TFIIIC-class transcription factor complex binding / TORC1 complex / voluntary musculoskeletal movement / positive regulation of transcription of nucleolar large rRNA by RNA polymerase I / calcineurin-NFAT signaling cascade / regulation of osteoclast differentiation / RNA polymerase III type 3 promoter sequence-specific DNA binding / positive regulation of keratinocyte migration / regulation of lysosome organization / MTOR signalling / Amino acids regulate mTORC1 / cellular response to nutrient / cellular response to L-leucine / energy reserve metabolic process / regulation of autophagosome assembly / Energy dependent regulation of mTOR by LKB1-AMPK / TORC1 signaling / ruffle organization / positive regulation by virus of viral protein levels in host cell / serine/threonine protein kinase complex / cellular response to methionine / spindle assembly involved in female meiosis / negative regulation of cell size / epigenetic programming in the zygotic pronuclei / positive regulation of ubiquitin-dependent protein catabolic process / inositol hexakisphosphate binding / cellular response to osmotic stress / UV-damage excision repair / anoikis / negative regulation of protein localization to nucleus / cardiac muscle cell development / negative regulation of calcineurin-NFAT signaling cascade / regulation of myelination / biological process involved in interaction with symbiont / regulation of mitotic cell cycle phase transition / positive regulation of transcription by RNA polymerase III / WD40-repeat domain binding / Cul4A-RING E3 ubiquitin ligase complex / Cul4-RING E3 ubiquitin ligase complex / negative regulation of macroautophagy / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / Macroautophagy / positive regulation of myotube differentiation / regulation of cell size / positive regulation of actin filament polymerization / Constitutive Signaling by AKT1 E17K in Cancer / negative regulation of reproductive process / negative regulation of developmental process / germ cell development / locomotory exploration behavior / TOR signaling / behavioral response to pain / cullin family protein binding / mTORC1-mediated signalling / oligodendrocyte differentiation / viral release from host cell / positive regulation of oligodendrocyte differentiation / positive regulation of translational initiation / CD28 dependent PI3K/Akt signaling / positive regulation of Wnt signaling pathway / HSF1-dependent transactivation / regulation of macroautophagy / ectopic germ cell programmed cell death / response to amino acid / 'de novo' pyrimidine nucleobase biosynthetic process / negative regulation of protein-containing complex assembly / positive regulation of epithelial to mesenchymal transition / heart morphogenesis / positive regulation of viral genome replication / vascular endothelial cell response to laminar fluid shear stress / neuronal action potential / positive regulation of lipid biosynthetic process / cellular response to nutrient levels / proteasomal protein catabolic process / regulation of cellular response to heat / positive regulation of lamellipodium assembly / cardiac muscle contraction / phagocytic vesicle / T cell costimulation / positive regulation of stress fiber assembly / cytoskeleton organization / positive regulation of gluconeogenesis / endomembrane system / negative regulation of autophagy / negative regulation of insulin receptor signaling pathway Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Petzold, G. / Trenh, P. / Bunker, R.D. / Tsai, J.H.C. | ||||||
Funding support | 1items
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![]() | ![]() Title: Mining the CRBN target space redefines rules for molecular glue-induced neosubstrate recognition. Authors: Petzold, G. / Gainza, P. / Annunziato, S. / Lamberto, I. / Trenh, P. / McAllister, L.A. / DeMarco, B. / Schwander, L. / Bunker, R.D. / Zlotosch, M. / SriRamaratnam, R. / Gilberto, S. / ...Authors: Petzold, G. / Gainza, P. / Annunziato, S. / Lamberto, I. / Trenh, P. / McAllister, L.A. / DeMarco, B. / Schwander, L. / Bunker, R.D. / Zlotosch, M. / SriRamaratnam, R. / Gilberto, S. / Langousis, G. / Donckele, E.J. / Quan, C. / Strande, V. / De Donatis, G.M. / Alabi, S.B. / Alers, J. / Matysik, M. / Staehly, C. / Dubois, A. / Osmont, A. / Garskovas, M. / Lyon, D. / Wiedmer, L. / Oleinikovas, V. / Lieberherr, R. / Rubin, N.T. / Lam, D.T. / Lucas, X. / Liardo, E. / Widlund, N.I. / Ritzen, A. / Caceres, R.M. / Vigil, D. / Tsai, J. / Wallace, O. / Peluso, M. / Sadok, A. / Tiedt, R. / Paterson, A.M. / Zarayskiy, V. / Fasching, B. / Bonenfant, D. / Warmuth, M. / Castle, J.C. / Townson, S.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 | ![]() | 599.7 KB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 732.5 KB | Display | ![]() |
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Full document | ![]() | 739 KB | Display | |
Data in XML | ![]() | 47.8 KB | Display | |
Data in CIF | ![]() | 62.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9nfqC ![]() 9nfrC C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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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: 127097.469 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Protein | Mass: 50603.676 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#3: Protein | Mass: 11803.489 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: P42345, non-specific serine/threonine protein kinase, non-specific protein-tyrosine kinase |
#4: Chemical | ChemComp-ZN / |
#5: Chemical | ChemComp-A1BC8 / ( Mass: 292.314 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C12H12N4O3S / Feature type: SUBJECT OF INVESTIGATION |
Has ligand of interest | Y |
Has protein modification | N |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 1.94 Å3/Da / Density % sol: 36.71 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop Details: 70 mM MES pH 6.0, 1.8-3.2 % (w/v) PEG 3,000, and 13-24 % (w/v) PEG 200 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: May 8, 2024 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.96546 Å / Relative weight: 1 |
Reflection | Resolution: 2.61→74.24 Å / Num. obs: 30713 / % possible obs: 96.5 % / Redundancy: 11 % / CC1/2: 0.997 / Rmerge(I) obs: 0.153 / Net I/σ(I): 10.9 |
Reflection shell | Resolution: 2.95→3.05 Å / Num. unique obs: 1372 / CC1/2: 0.438 |
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Processing
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Refinement | Method to determine structure: ![]() Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 85.42 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.95→43.78 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group | Refine-ID: X-RAY DIFFRACTION
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