+Open data
-Basic information
Entry | Database: PDB / ID: 6xog | ||||||
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Title | Structure of SUMO1-ML786519 adduct bound to SAE | ||||||
Components |
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Keywords | LIGASE/LIGASE inhibitor / SAE / SUMO1 / covalent inhibitor / LIGASE / LIGASE-LIGASE inhibitor complex | ||||||
Function / homology | Function and homology information SUMO activating enzyme complex / SUMO activating enzyme activity / ubiquitin activating enzyme activity / negative regulation of transcription by transcription factor localization / SUMOylation of nuclear envelope proteins / Negative regulation of activity of TFAP2 (AP-2) family transcription factors / SUMO is proteolytically processed / negative regulation of delayed rectifier potassium channel activity / SUMO is conjugated to E1 (UBA2:SAE1) / nuclear stress granule ...SUMO activating enzyme complex / SUMO activating enzyme activity / ubiquitin activating enzyme activity / negative regulation of transcription by transcription factor localization / SUMOylation of nuclear envelope proteins / Negative regulation of activity of TFAP2 (AP-2) family transcription factors / SUMO is proteolytically processed / negative regulation of delayed rectifier potassium channel activity / SUMO is conjugated to E1 (UBA2:SAE1) / nuclear stress granule / SUMO is transferred from E1 to E2 (UBE2I, UBC9) / negative regulation of action potential / SUMO binding / small protein activating enzyme binding / positive regulation of protein sumoylation / SUMOylation of DNA methylation proteins / SUMOylation of SUMOylation proteins / SUMOylation of immune response proteins / ATP-dependent protein binding / Maturation of nucleoprotein / Transferases; Acyltransferases; Aminoacyltransferases / SUMOylation of RNA binding proteins / ubiquitin-like protein conjugating enzyme binding / Postmitotic nuclear pore complex (NPC) reformation / Maturation of nucleoprotein / positive regulation of protein targeting to mitochondrion / negative regulation of protein import into nucleus / ubiquitin-specific protease binding / SUMOylation of ubiquitinylation proteins / roof of mouth development / negative regulation of DNA binding / ubiquitin-like protein ligase binding / SUMOylation of DNA replication proteins / protein sumoylation / transcription factor binding / SUMOylation of transcription factors / enzyme activator activity / potassium channel regulator activity / SUMOylation of DNA damage response and repair proteins / nuclear pore / Regulation of IFNG signaling / cellular response to cadmium ion / SUMOylation of chromatin organization proteins / SUMOylation of transcription cofactors / positive regulation of protein-containing complex assembly / SUMOylation of intracellular receptors / PKR-mediated signaling / negative regulation of DNA-binding transcription factor activity / PML body / protein tag activity / Formation of Incision Complex in GG-NER / regulation of protein localization / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / cellular response to heat / transferase activity / nuclear membrane / protein stabilization / nuclear body / nuclear speck / protein heterodimerization activity / DNA repair / negative regulation of DNA-templated transcription / ubiquitin protein ligase binding / nucleolus / enzyme binding / magnesium ion binding / RNA binding / nucleoplasm / ATP binding / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.98 Å | ||||||
Authors | Sintchak, M. / Lane, W. / Bump, N. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2021 Title: Discovery of TAK-981, a First-in-Class Inhibitor of SUMO-Activating Enzyme for the Treatment of Cancer. Authors: Langston, S.P. / Grossman, S. / England, D. / Afroze, R. / Bence, N. / Bowman, D. / Bump, N. / Chau, R. / Chuang, B.C. / Claiborne, C. / Cohen, L. / Connolly, K. / Duffey, M. / Durvasula, N. ...Authors: Langston, S.P. / Grossman, S. / England, D. / Afroze, R. / Bence, N. / Bowman, D. / Bump, N. / Chau, R. / Chuang, B.C. / Claiborne, C. / Cohen, L. / Connolly, K. / Duffey, M. / Durvasula, N. / Freeze, S. / Gallery, M. / Galvin, K. / Gaulin, J. / Gershman, R. / Greenspan, P. / Grieves, J. / Guo, J. / Gulavita, N. / Hailu, S. / He, X. / Hoar, K. / Hu, Y. / Hu, Z. / Ito, M. / Kim, M.S. / Lane, S.W. / Lok, D. / Lublinsky, A. / Mallender, W. / McIntyre, C. / Minissale, J. / Mizutani, H. / Mizutani, M. / Molchinova, N. / Ono, K. / Patil, A. / Qian, M. / Riceberg, J. / Shindi, V. / Sintchak, M.D. / Song, K. / Soucy, T. / Wang, Y. / Xu, H. / Yang, X. / Zawadzka, A. / Zhang, J. / Pulukuri, S.M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6xog.cif.gz | 194.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6xog.ent.gz | 146.1 KB | Display | PDB format |
PDBx/mmJSON format | 6xog.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xo/6xog ftp://data.pdbj.org/pub/pdb/validation_reports/xo/6xog | HTTPS FTP |
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-Related structure data
Related structure data | 6xohC 6xoiC 1y8rS 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
-SUMO-activating enzyme subunit ... , 2 types, 2 molecules AB
#1: Protein | Mass: 38499.789 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SAE1, AOS1, SUA1, UBLE1A / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q9UBE0 |
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#2: Protein | Mass: 71314.508 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: UBA2, SAE2, UBLE1B, HRIHFB2115 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: Q9UBT2, Transferases; Acyltransferases; Aminoacyltransferases |
-Protein , 1 types, 1 molecules C
#3: Protein | Mass: 11575.005 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SUMO1, SMT3C, SMT3H3, UBL1, OK/SW-cl.43 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63165 |
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-Non-polymers , 4 types, 257 molecules
#4: Chemical | ChemComp-SO4 / |
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#5: Chemical | ChemComp-ZN / |
#6: Chemical | ChemComp-VAY / {( |
#7: Water | ChemComp-HOH / |
-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: 2.19 Å3/Da / Density % sol: 43.74 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion Details: 50 mM BisTris, pH 6.5, 50 mM Ammonium Sulfate, 30% pentaerythritol ethoxylate (Hampton Index 57) |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: CLSI / Beamline: 08ID-1 / Wavelength: 0.97949 Å |
Detector | Type: RAYONIX MX-300 / Detector: CCD / Date: May 29, 2013 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97949 Å / Relative weight: 1 |
Reflection | Resolution: 1.98→47.702 Å / Num. obs: 71980 / % possible obs: 98.47 % / Redundancy: 3.7 % / Rsym value: 0.093 / Net I/σ(I): 25.7 |
Reflection shell | Resolution: 1.98→2.05 Å / Mean I/σ(I) obs: 2.37 / Num. unique obs: 7068 / Rsym value: 0.818 / % possible all: 97.15 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1Y8R Resolution: 1.98→47.702 Å / Cor.coef. Fo:Fc: 0.954 / Cor.coef. Fo:Fc free: 0.934 / WRfactor Rfree: 0.239 / WRfactor Rwork: 0.206 / Average fsc free: 0.8974 / Average fsc work: 0.9082 / Cross valid method: FREE R-VALUE / ESU R: 0.173 / ESU R Free: 0.155 Details: Hydrogens have been added in their 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 / Solvent model: MASK BULK SOLVENT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 45.146 Å2
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Refinement step | Cycle: LAST / Resolution: 1.98→47.702 Å
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Refine LS restraints |
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LS refinement shell |
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