[English] 日本語
Yorodumi
- PDB-3gzn: Structure of NEDD8-activating enzyme in complex with NEDD8 and MLN4924 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3gzn
TitleStructure of NEDD8-activating enzyme in complex with NEDD8 and MLN4924
Components
  • NEDD8
  • NEDD8-activating enzyme E1 catalytic subunit
  • NEDD8-activating enzyme E1 regulatory subunit
KeywordsPROTEIN BINDING/Ligase / NEDD8 / E1-activating enzyme / MLN4924 / PROTEIN BINDING-Ligase complex
Function / homology
Function and homology information


E1 NEDD8-activating enzyme / NEDD8 activating enzyme activity / endomitotic cell cycle / NEDD8 transferase activity / mitotic DNA replication checkpoint signaling / protein neddylation / TGF-beta receptor signaling activates SMADs / regulation of proteolysis / regulation of postsynapse assembly / anatomical structure morphogenesis ...E1 NEDD8-activating enzyme / NEDD8 activating enzyme activity / endomitotic cell cycle / NEDD8 transferase activity / mitotic DNA replication checkpoint signaling / protein neddylation / TGF-beta receptor signaling activates SMADs / regulation of proteolysis / regulation of postsynapse assembly / anatomical structure morphogenesis / regulation of neuron apoptotic process / post-translational protein modification / NIK-->noncanonical NF-kB signaling / Dectin-1 mediated noncanonical NF-kB signaling / Iron uptake and transport / protein modification process / modification-dependent protein catabolic process / protein tag activity / UCH proteinases / intracellular protein localization / Antigen processing: Ubiquitination & Proteasome degradation / Cargo recognition for clathrin-mediated endocytosis / Neddylation / neuron apoptotic process / ubiquitin-dependent protein catabolic process / regulation of apoptotic process / regulation of cell cycle / postsynapse / protein heterodimerization activity / ubiquitin protein ligase binding / regulation of transcription by RNA polymerase II / glutamatergic synapse / signal transduction / protein-containing complex / proteolysis / extracellular exosome / nucleoplasm / ATP binding / identical protein binding / nucleus / plasma membrane / cytoplasm / cytosol
Similarity search - Function
NEDD8-activating enzyme E1, catalytic subunit / NEDD8-activating enzyme E1 regulatory subunit APP-BP1 / E2 binding / NEDD8-activating enzyme E1 catalytic subunit / E2 binding domain / E2_bind / Ubiquitin activating enzymes (Uba3). Chain: B, domain 2 / Ubiquitin activating enzyme, alpha domain superfamily / Nedd8-like ubiquitin / Ubiquitin-activating enzyme E1, Cys active site ...NEDD8-activating enzyme E1, catalytic subunit / NEDD8-activating enzyme E1 regulatory subunit APP-BP1 / E2 binding / NEDD8-activating enzyme E1 catalytic subunit / E2 binding domain / E2_bind / Ubiquitin activating enzymes (Uba3). Chain: B, domain 2 / Ubiquitin activating enzyme, alpha domain superfamily / Nedd8-like ubiquitin / Ubiquitin-activating enzyme E1, Cys active site / Ubiquitin-activating enzyme active site. / ThiF/MoeB/HesA family / THIF-type NAD/FAD binding fold / ThiF family / Ubiquitin-activating enzyme / Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, domain 1 / : / Ubiquitin domain signature. / Ubiquitin conserved site / Ubiquitin domain / Ubiquitin-like (UB roll) / Ubiquitin family / Ubiquitin homologues / Ubiquitin domain profile. / Ubiquitin-like domain / Arc Repressor Mutant, subunit A / NAD(P)-binding Rossmann-like Domain / Ubiquitin-like domain superfamily / Roll / Rossmann fold / Orthogonal Bundle / 3-Layer(aba) Sandwich / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-B39 / NEDD8-activating enzyme E1 regulatory subunit / Ubiquitin-like protein NEDD8 / NEDD8-activating enzyme E1 catalytic subunit
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3 Å
AuthorsSintchak, M.D.
CitationJournal: Mol.Cell / Year: 2010
Title: Substrate-assisted inhibition of ubiquitin-like protein-activating enzymes: the NEDD8 E1 inhibitor MLN4924 forms a NEDD8-AMP mimetic in situ.
Authors: Brownell, J.E. / Sintchak, M.D. / Gavin, J.M. / Liao, H. / Bruzzese, F.J. / Bump, N.J. / Soucy, T.A. / Milhollen, M.A. / Yang, X. / Burkhardt, A.L. / Ma, J. / Loke, H.K. / Lingaraj, T. / Wu, ...Authors: Brownell, J.E. / Sintchak, M.D. / Gavin, J.M. / Liao, H. / Bruzzese, F.J. / Bump, N.J. / Soucy, T.A. / Milhollen, M.A. / Yang, X. / Burkhardt, A.L. / Ma, J. / Loke, H.K. / Lingaraj, T. / Wu, D. / Hamman, K.B. / Spelman, J.J. / Cullis, C.A. / Langston, S.P. / Vyskocil, S. / Sells, T.B. / Mallender, W.D. / Visiers, I. / Li, P. / Claiborne, C.F. / Rolfe, M. / Bolen, J.B. / Dick, L.R.
History
DepositionApr 7, 2009Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 2, 2010Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Mar 21, 2012Group: Database references
Revision 1.3Sep 6, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / pdbx_struct_conn_angle / struct_conn / struct_conn_type / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_conn_angle.ptnr1_auth_asym_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr2_auth_asym_id / _pdbx_struct_conn_angle.ptnr2_label_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.conn_type_id / _struct_conn.id / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn_type.id / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.4Nov 20, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: NEDD8-activating enzyme E1 regulatory subunit
B: NEDD8-activating enzyme E1 catalytic subunit
C: NEDD8-activating enzyme E1 regulatory subunit
D: NEDD8-activating enzyme E1 catalytic subunit
I: NEDD8
J: NEDD8
hetero molecules


Theoretical massNumber of molelcules
Total (without water)244,26610
Polymers243,2486
Non-polymers1,0184
Water00
1
A: NEDD8-activating enzyme E1 regulatory subunit
B: NEDD8-activating enzyme E1 catalytic subunit
I: NEDD8
hetero molecules


Theoretical massNumber of molelcules
Total (without water)122,1335
Polymers121,6243
Non-polymers5092
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area10080 Å2
ΔGint-36 kcal/mol
Surface area41380 Å2
MethodPISA
2
C: NEDD8-activating enzyme E1 regulatory subunit
D: NEDD8-activating enzyme E1 catalytic subunit
J: NEDD8
hetero molecules


Theoretical massNumber of molelcules
Total (without water)122,1335
Polymers121,6243
Non-polymers5092
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area10090 Å2
ΔGint-35 kcal/mol
Surface area41220 Å2
MethodPISA
Unit cell
Length a, b, c (Å)135.030, 228.715, 229.307
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number23
Space group name H-MI222

-
Components

#1: Protein NEDD8-activating enzyme E1 regulatory subunit / Amyloid protein-binding protein 1 / Amyloid beta precursor protein-binding protein 1 / 59 kDa / APP- ...Amyloid protein-binding protein 1 / Amyloid beta precursor protein-binding protein 1 / 59 kDa / APP-BP1 / Proto-oncogene protein 1


Mass: 60315.102 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: APPBP1, HPP1, NAE1 / Production host: Spodoptera frugiperda (fall armyworm) / Strain (production host): Sf9 / References: UniProt: Q13564
#2: Protein NEDD8-activating enzyme E1 catalytic subunit / Ubiquitin-like modifier-activating enzyme 3 / Ubiquitin-activating enzyme 3 / NEDD8-activating ...Ubiquitin-like modifier-activating enzyme 3 / Ubiquitin-activating enzyme 3 / NEDD8-activating enzyme E1C / Ubiquitin-activating enzyme E1C


Mass: 51906.180 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: UBA3, UBE1C / Production host: Spodoptera frugiperda (fall armyworm) / Strain (production host): Sf9
References: UniProt: Q8TBC4, Ligases; Forming carbon-nitrogen bonds; Acid-amino-acid ligases (peptide synthases)
#3: Protein NEDD8 / Ubiquitin-like protein Nedd8 / Neddylin / Neural precursor cell expressed developmentally down- ...Ubiquitin-like protein Nedd8 / Neddylin / Neural precursor cell expressed developmentally down-regulated protein 8 / NEDD-8


Mass: 9402.857 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NEDD8 / Production host: Spodoptera frugiperda (fall armyworm) / Strain (production host): Sf9 / References: UniProt: Q15843
#4: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#5: Chemical ChemComp-B39 / [(1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl]methyl sulfamate


Mass: 443.519 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C21H25N5O4S
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION

-
Sample preparation

CrystalDensity Matthews: 3.62 Å3/Da / Density % sol: 66.06 %
Crystal growTemperature: 293 K
Details: 1.8 M tri-ammonium citrate pH 7.0, 4% (v/v) 1,3 butanediol, temperature 293K

-
Data collection

DiffractionMean temperature: 93 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 31-ID / Wavelength: 0.97929 Å
DetectorType: MAR CCD 165 mm / Detector: CCD / Date: Feb 16, 2008
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97929 Å / Relative weight: 1
ReflectionResolution: 3→49.36 Å / % possible obs: 92.3 % / Redundancy: 5.9 % / Rmerge(I) obs: 0.094 / Net I/σ(I): 15.9

-
Processing

SoftwareName: REFMAC / Version: 5.2.0005 / Classification: refinement
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1R4M

1r4m


Resolution: 3→49.36 Å / Cor.coef. Fo:Fc: 0.926 / Cor.coef. Fo:Fc free: 0.887 / SU B: 18.24 / SU ML: 0.336 / Cross valid method: THROUGHOUT / ESU R: 2.059 / ESU R Free: 0.435 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.28702 3515 5 %RANDOM
Rwork0.23046 ---
obs0.23325 66102 97.87 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso mean: 66.768 Å2
Baniso -1Baniso -2Baniso -3
1-6.91 Å20 Å20 Å2
2---3.48 Å20 Å2
3----3.43 Å2
Refinement stepCycle: LAST / Resolution: 3→49.36 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms15986 0 64 0 16050
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0080.02216389
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.1471.96422294
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.66252060
X-RAY DIFFRACTIONr_dihedral_angle_2_deg38.56824.772746
X-RAY DIFFRACTIONr_dihedral_angle_3_deg17.111152663
X-RAY DIFFRACTIONr_dihedral_angle_4_deg15.8841585
X-RAY DIFFRACTIONr_chiral_restr0.080.22540
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.02112493
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined0.2110.27573
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined0.3080.211181
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1530.2466
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.1780.238
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.1260.21
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it0.577210315
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it1.086316612
X-RAY DIFFRACTIONr_scbond_it0.87136074
X-RAY DIFFRACTIONr_scangle_it1.44545682
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 3→3.079 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.386 262 -
Rwork0.308 4811 -
obs--96.81 %

+
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