[English] 日本語
Yorodumi
- PDB-6xoh: Structure of SUMO1-ML00789344 adduct bound to SAE -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6xoh
TitleStructure of SUMO1-ML00789344 adduct bound to SAE
Components
  • (SUMO-activating enzyme subunit ...) x 2
  • Small ubiquitin-related modifier 1
KeywordsLIGASE/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
SUMO-activating enzyme subunit 2, C-terminal domain / SUMO-activating enzyme subunit 2 C-terminus / Ubiquitin/SUMO-activating enzyme ubiquitin-like domain / Ubiquitin/SUMO-activating enzyme ubiquitin-like domain / SUMO-activating enzyme subunit Uba2 / Ubiquitin activating enzyme, alpha domain superfamily / Ubiquitin-activating enzyme E1, conserved site / Ubiquitin-activating enzyme signature 1. / Ubiquitin/SUMO-activating enzyme E1-like / Ubiquitin-activating enzyme E1, inactive adenylation domain, subdomain 1 ...SUMO-activating enzyme subunit 2, C-terminal domain / SUMO-activating enzyme subunit 2 C-terminus / Ubiquitin/SUMO-activating enzyme ubiquitin-like domain / Ubiquitin/SUMO-activating enzyme ubiquitin-like domain / SUMO-activating enzyme subunit Uba2 / Ubiquitin activating enzyme, alpha domain superfamily / Ubiquitin-activating enzyme E1, conserved site / Ubiquitin-activating enzyme signature 1. / Ubiquitin/SUMO-activating enzyme E1-like / Ubiquitin-activating enzyme E1, inactive adenylation domain, subdomain 1 / Small ubiquitin-related modifier 1, Ubl domain / Ubiquitin-activating enzyme E1, Cys active site / Ubiquitin-activating enzyme active site. / ThiF/MoeB/HesA family / Ubiquitin-activating enzyme / THIF-type NAD/FAD binding fold / ThiF family / Rad60/SUMO-like domain / Ubiquitin-2 like Rad60 SUMO-like / Ubiquitin homologues / Ubiquitin-like domain / Ubiquitin domain profile. / Ubiquitin-like domain superfamily
Similarity search - Domain/homology
Chem-VB7 / Small ubiquitin-related modifier 1 / SUMO-activating enzyme subunit 1 / SUMO-activating enzyme subunit 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.226 Å
AuthorsSintchak, M. / Lane, W. / Bump, N.
CitationJournal: 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
DepositionJul 7, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 24, 2021Provider: repository / Type: Initial release
Revision 1.1Oct 18, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: SUMO-activating enzyme subunit 1
B: SUMO-activating enzyme subunit 2
C: Small ubiquitin-related modifier 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)122,0816
Polymers121,3893
Non-polymers6923
Water3,387188
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area7850 Å2
ΔGint-53 kcal/mol
Surface area35220 Å2
MethodPISA
Unit cell
Length a, b, c (Å)58.133, 72.947, 126.586
Angle α, β, γ (deg.)90.000, 92.933, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

-
SUMO-activating enzyme subunit ... , 2 types, 2 molecules AB

#1: Protein SUMO-activating enzyme subunit 1 / Ubiquitin-like 1-activating enzyme E1A


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
#2: Protein SUMO-activating enzyme subunit 2 / Anthracycline-associated resistance ARX / Ubiquitin-like 1-activating enzyme E1B / Ubiquitin-like ...Anthracycline-associated resistance ARX / Ubiquitin-like 1-activating enzyme E1B / Ubiquitin-like modifier-activating enzyme 2


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 Small ubiquitin-related modifier 1 / SUMO-1 / GAP-modifying protein 1 / GMP1 / SMT3 homolog 3 / Sentrin / Ubiquitin-homology domain ...SUMO-1 / GAP-modifying protein 1 / GMP1 / SMT3 homolog 3 / Sentrin / Ubiquitin-homology domain protein PIC1 / Ubiquitin-like protein SMT3C / Smt3C / Ubiquitin-like protein UBL1


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

-
Non-polymers , 4 types, 191 molecules

#4: Chemical ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#5: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#6: Chemical ChemComp-VB7 / {(1R,2S,4R)-4-[(5-{4-[(1R)-3,4-dihydro-1H-2-benzopyran-1-yl]thiophene-2-carbonyl}pyrimidin-4-yl)amino]-2-hydroxycyclopentyl}methyl sulfamate


Mass: 530.616 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C24H26N4O6S2 / Feature type: SUBJECT OF INVESTIGATION
#7: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 188 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.21 Å3/Da / Density % sol: 44.3 %
Crystal growTemperature: 293 K / Method: vapor diffusion
Details: 50 mM BisTris, pH 6.5, 50 mM Ammonium Sulfate, 30% pentaerythritol ethoxylate (Hampton Index 57)

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: CLSI / Beamline: 08ID-1 / Wavelength: 0.9795 Å
DetectorType: RAYONIX MX-300 / Detector: CCD / Date: Sep 29, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 2.226→47.004 Å / Num. obs: 50291 / % possible obs: 97.02 % / Redundancy: 3.7 % / Rsym value: 0.064 / Net I/σ(I): 18.48
Reflection shellResolution: 2.23→2.31 Å / Mean I/σ(I) obs: 2 / Num. unique obs: 4828 / Rsym value: 0.664

-
Processing

Software
NameVersionClassification
REFMAC5.8.0258refinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1Y8R

1y8r


Resolution: 2.226→43.31 Å / Cor.coef. Fo:Fc: 0.96 / Cor.coef. Fo:Fc free: 0.933 / SU B: 6.729 / SU ML: 0.166 / Cross valid method: FREE R-VALUE / ESU R: 0.252 / ESU R Free: 0.209
Details: Hydrogens have been added in their riding positions
RfactorNum. reflection% reflection
Rfree0.2436 2554 5.078 %
Rwork0.1939 47737 -
all0.196 --
obs-50291 96.613 %
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK BULK SOLVENT
Displacement parametersBiso mean: 63.594 Å2
Baniso -1Baniso -2Baniso -3
1--0.308 Å20 Å22.042 Å2
2--0.534 Å20 Å2
3----0.433 Å2
Refinement stepCycle: LAST / Resolution: 2.226→43.31 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6479 0 42 188 6709
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0070.0126638
X-RAY DIFFRACTIONr_angle_refined_deg1.4771.6378999
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.8915839
X-RAY DIFFRACTIONr_dihedral_angle_2_deg33.35623.17306
X-RAY DIFFRACTIONr_dihedral_angle_3_deg18.508151097
X-RAY DIFFRACTIONr_dihedral_angle_4_deg16.4671532
X-RAY DIFFRACTIONr_chiral_restr0.1080.2896
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.024955
X-RAY DIFFRACTIONr_nbd_refined0.2250.22993
X-RAY DIFFRACTIONr_nbtor_refined0.3140.24506
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1560.2305
X-RAY DIFFRACTIONr_symmetry_nbd_refined0.1940.216
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_refined0.0840.23
X-RAY DIFFRACTIONr_mcbond_it5.3176.5263401
X-RAY DIFFRACTIONr_mcangle_it7.7139.7254225
X-RAY DIFFRACTIONr_scbond_it6.0916.7393237
X-RAY DIFFRACTIONr_scangle_it8.4989.9744774
X-RAY DIFFRACTIONr_lrange_it11.37587.239819
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 20

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRfactor allNum. reflection allFsc freeFsc work% reflection obs (%)WRfactor Rwork
2.226-2.2840.3291620.28631960.28838180.7810.79387.95180.261
2.284-2.3460.2841980.24733890.24937280.8470.85796.21780.216
2.346-2.4140.2931660.25133160.25336220.8350.85696.13470.216
2.414-2.4880.281710.23432070.23634860.8570.87396.90190.203
2.488-2.5690.281460.21631310.21934140.8740.90195.98710.184
2.569-2.6590.2932020.22229830.22633250.8690.90195.78950.189
2.659-2.7590.2611540.20929320.21231970.9020.91996.5280.187
2.759-2.8720.2711400.20528000.20830270.8890.91997.12590.185
2.872-2.9990.2541410.20827470.2129670.8990.92197.33740.192
2.999-3.1450.3251420.22326100.22928090.8760.90497.97080.216
3.145-3.3140.2391300.19725220.19927020.9150.9398.14950.197
3.314-3.5140.2311420.19623650.19825450.9250.93598.50690.203
3.514-3.7550.2561040.18722500.1923910.9220.9498.45250.201
3.755-4.0540.2021190.17721080.17822550.9450.95198.75830.193
4.054-4.4370.2031270.15519030.15820600.9440.96198.54370.176
4.437-4.9550.195970.14517280.14818550.9540.96498.38270.172
4.955-5.7120.254690.18215720.18516630.9160.94798.67710.213
5.712-6.9690.23600.21313300.21414040.9280.9299.00290.251
6.969-9.750.208540.1710530.17211210.9590.96598.75110.221
9.75-47.0040.3300.2175950.2216520.9020.94195.85890.283

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more