[English] 日本語
Yorodumi
- PDB-6xog: Structure of SUMO1-ML786519 adduct bound to SAE -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6xog
TitleStructure of SUMO1-ML786519 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 activity / SUMO activating enzyme complex / negative regulation of potassium ion transmembrane transporter activity / protein localization to nuclear pore / : / SUMOylation of nuclear envelope proteins / ubiquitin activating enzyme activity / SUMO is proteolytically processed / Negative regulation of activity of TFAP2 (AP-2) family transcription factors / SUMO is conjugated to E1 (UBA2:SAE1) ...SUMO activating enzyme activity / SUMO activating enzyme complex / negative regulation of potassium ion transmembrane transporter activity / protein localization to nuclear pore / : / SUMOylation of nuclear envelope proteins / ubiquitin activating enzyme activity / SUMO is proteolytically processed / Negative regulation of activity of TFAP2 (AP-2) family transcription factors / SUMO is conjugated to E1 (UBA2:SAE1) / negative regulation of delayed rectifier potassium channel activity / PML body organization / negative regulation of DNA binding / SUMO is transferred from E1 to E2 (UBE2I, UBC9) / negative regulation of action potential / nuclear stress granule / SUMO binding / positive regulation of protein sumoylation / small protein activating enzyme binding / SUMOylation of DNA methylation proteins / SUMOylation of immune response proteins / SUMOylation of SUMOylation proteins / XY body / regulation of calcium ion transmembrane transport / ATP-dependent protein binding / Maturation of nucleoprotein / SUMOylation of RNA binding proteins / Transferases; Acyltransferases; Aminoacyltransferases / regulation of cardiac muscle cell contraction / Postmitotic nuclear pore complex (NPC) reformation / positive regulation of protein targeting to mitochondrion / Maturation of nucleoprotein / ubiquitin-like protein conjugating enzyme binding / negative regulation of protein import into nucleus / SUMOylation of ubiquitinylation proteins / transcription factor binding / ubiquitin-specific protease binding / cellular response to cadmium ion / roof of mouth development / SUMOylation of transcription factors / ubiquitin-like protein ligase binding / SUMOylation of DNA replication proteins / protein sumoylation / potassium channel regulator activity / Regulation of IFNG signaling / postsynaptic cytosol / transporter activator activity / nuclear pore / negative regulation of DNA-binding transcription factor activity / SUMOylation of DNA damage response and repair proteins / presynaptic cytosol / Transcriptional and post-translational regulation of MITF-M expression and activity / SUMOylation of transcription cofactors / SUMOylation of chromatin organization proteins / positive regulation of protein-containing complex assembly / SUMOylation of intracellular receptors / enzyme activator activity / PML body / PKR-mediated signaling / regulation of protein stability / Formation of Incision Complex in GG-NER / protein tag activity / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / regulation of protein localization / transferase activity / cellular response to heat / nuclear membrane / protein stabilization / nuclear speck / nuclear body / protein heterodimerization activity / DNA repair / negative regulation of DNA-templated transcription / ubiquitin protein ligase binding / nucleolus / glutamatergic synapse / enzyme binding / magnesium ion binding / RNA binding / nucleoplasm / ATP binding / nucleus / plasma membrane / cytoplasm / cytosol
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. / Small ubiquitin-related modifier 1, Ubl domain / Ubiquitin-activating enzyme E1, Cys active site ...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. / Small ubiquitin-related modifier 1, Ubl domain / Ubiquitin-activating enzyme E1, Cys active site / Ubiquitin-activating enzyme active site. / Ubiquitin/SUMO-activating enzyme E1-like / Ubiquitin-activating enzyme E1, inactive adenylation domain, subdomain 1 / ThiF/MoeB/HesA family / THIF-type NAD/FAD binding fold / ThiF family / Ubiquitin-activating enzyme / Rad60/SUMO-like domain / Ubiquitin-2 like Rad60 SUMO-like / Ubiquitin homologues / Ubiquitin domain profile. / Ubiquitin-like domain / Ubiquitin-like domain superfamily
Similarity search - Domain/homology
Chem-VAY / 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: 1.98 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 10, 2021Provider: repository / Type: Initial release
Revision 1.1Mar 24, 2021Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.2Oct 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
Revision 1.3Nov 6, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
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)122,1656
Polymers121,3893
Non-polymers7763
Water4,576254
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area7960 Å2
ΔGint-53 kcal/mol
Surface area36250 Å2
MethodPISA
Unit cell
Length a, b, c (Å)57.900, 72.422, 126.870
Angle α, β, γ (deg.)90.000, 93.858, 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, 257 molecules

#4: Chemical ChemComp-SO4 / SULFATE ION


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-VAY / {(1R,2R,3S,4R)-4-[(5-{4-[(1S)-1-(6-bromopyridin-2-yl)-1-hydroxyethyl]thiophene-2-carbonyl}pyrimidin-4-yl)amino]-2,3-dihydroxycyclopentyl}methyl sulfamate


Mass: 614.489 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C22H24BrN5O7S2 / Feature type: SUBJECT OF INVESTIGATION
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 254 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.19 Å3/Da / Density % sol: 43.74 %
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: 0.97949 Å
DetectorType: RAYONIX MX-300 / Detector: CCD / Date: May 29, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97949 Å / Relative weight: 1
ReflectionResolution: 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 shellResolution: 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
NameVersionClassification
REFMAC5.8.0258refinement
XDSdata reduction
XDSdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1Y8R

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
RfactorNum. reflection% reflection
Rfree0.24 3655 5.078 %
Rwork0.2064 68325 -
all0.208 --
obs-71980 98.465 %
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: 45.146 Å2
Baniso -1Baniso -2Baniso -3
1-0.075 Å20 Å20.632 Å2
2--0.67 Å20 Å2
3----0.822 Å2
Refinement stepCycle: LAST / Resolution: 1.98→47.702 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6634 0 43 254 6931
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0090.0126794
X-RAY DIFFRACTIONr_angle_refined_deg1.6171.6389215
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.4625858
X-RAY DIFFRACTIONr_dihedral_angle_2_deg33.33723.408314
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.53151120
X-RAY DIFFRACTIONr_dihedral_angle_4_deg17.7361531
X-RAY DIFFRACTIONr_chiral_restr0.1420.2918
X-RAY DIFFRACTIONr_gen_planes_refined0.0080.025080
X-RAY DIFFRACTIONr_nbd_refined0.2280.23096
X-RAY DIFFRACTIONr_nbtor_refined0.3170.24645
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1590.2325
X-RAY DIFFRACTIONr_symmetry_nbd_refined0.1590.221
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_refined0.1740.28
X-RAY DIFFRACTIONr_mcbond_it4.2524.5113477
X-RAY DIFFRACTIONr_mcangle_it5.9036.7144320
X-RAY DIFFRACTIONr_scbond_it5.2744.8143317
X-RAY DIFFRACTIONr_scangle_it7.4587.0734895
X-RAY DIFFRACTIONr_lrange_it9.89261.10610104
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.98-2.0310.2932540.2854927X-RAY DIFFRACTION96.7146
2.031-2.0870.2742410.2584921X-RAY DIFFRACTION98.4175
2.087-2.1470.3132480.254777X-RAY DIFFRACTION98.4908
2.147-2.2130.2892630.2434617X-RAY DIFFRACTION98.7654
2.213-2.2860.2792490.234479X-RAY DIFFRACTION98.8294
2.286-2.3660.2362580.2154328X-RAY DIFFRACTION98.7936
2.366-2.4550.2832150.2234189X-RAY DIFFRACTION99.0108
2.455-2.5550.2452410.2234047X-RAY DIFFRACTION99.0529
2.555-2.6680.2562300.2213893X-RAY DIFFRACTION99.0154
2.668-2.7980.231850.2123726X-RAY DIFFRACTION99.1381
2.798-2.9480.2961860.2153552X-RAY DIFFRACTION99.0986
2.948-3.1270.2831670.2333375X-RAY DIFFRACTION99.1601
3.127-3.3410.2471570.2153181X-RAY DIFFRACTION98.7866
3.341-3.6080.2221520.2062948X-RAY DIFFRACTION98.8205
3.608-3.950.2161440.1882699X-RAY DIFFRACTION98.6126
3.95-4.4120.2091300.162454X-RAY DIFFRACTION97.953
4.412-5.0880.1591220.1522134X-RAY DIFFRACTION97.8742
5.088-6.2130.265850.21860X-RAY DIFFRACTION98.0343
6.213-8.7130.232870.2081413X-RAY DIFFRACTION97.6563
8.713-47.7020.207410.189799X-RAY DIFFRACTION91.3044

+
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