6SC8

dAb3/HOIP-RBR-Ligand4


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.11 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.221 

wwPDB Validation 3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Single-Domain Antibodies as Crystallization Chaperones to Enable Structure-Based Inhibitor Development for RBR E3 Ubiquitin Ligases.

Tsai, Y.I.Johansson, H.Dixon, D.Martin, S.Chung, C.W.Clarkson, J.House, D.Rittinger, K.

(2020) Cell Chem Biol 27: 83

  • DOI: 10.1016/j.chembiol.2019.11.007
  • Structures With Same Primary Citation

  • PubMed Abstract: 
  • Protein ubiquitination plays a key role in the regulation of cellular processes, and misregulation of the ubiquitin system is linked to many diseases. So far, development of tool compounds that target enzymes of the ubiquitin system has been slow and ...

    Protein ubiquitination plays a key role in the regulation of cellular processes, and misregulation of the ubiquitin system is linked to many diseases. So far, development of tool compounds that target enzymes of the ubiquitin system has been slow and only a few specific inhibitors are available. Here, we report the selection of single-domain antibodies (single-dAbs) based on a human scaffold that recognize the catalytic domain of HOIP, a subunit of the multi-component E3 LUBAC and member of the RBR family of E3 ligases. Some of these dAbs affect ligase activity and provide mechanistic insight into the ubiquitin transfer mechanism of different E2-conjugating enzymes. Furthermore, we show that the co-crystal structure of a HOIP RBR/dAb complex serves as a robust platform for soaking of ligands that target the active site cysteine of HOIP, thereby providing easy access to structure-based ligand design for this important class of E3 ligases.


    Organizational Affiliation

    Molecular Structure of Cell Signalling Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address: katrin.rittinger@crick.ac.uk.



Macromolecules

Find similar proteins by: Sequence  |  Structure

Entity ID: 1
MoleculeChainsSequence LengthOrganismDetails
E3 ubiquitin-protein ligase RNF31
A
376Homo sapiensMutation(s): 0 
Gene Names: RNF31ZIBRA
EC: 2.3.2.31
Find proteins for Q96EP0 (Homo sapiens)
Go to UniProtKB:  Q96EP0
NIH Common Fund Data Resources
PHAROS  Q96EP0

Find similar proteins by: Sequence  |  Structure

Entity ID: 2
MoleculeChainsSequence LengthOrganismDetails
Single domain antibody
B, C
120synthetic constructMutation(s): 0 
Protein Feature View is not available: No corresponding UniProt sequence found.
Small Molecules
Ligands 4 Unique
IDChainsName / Formula / InChI Key2D Diagram3D Interactions
L6E
Query on L6E

Download CCD File 
A
[2-(methylamino)-2-oxidanylidene-ethyl] (~{E})-4-[(2-oxidanylidene-5,6,7,8-tetrahydro-1~{H}-quinolin-3-yl)carbonylamino]but-2-enoate
C17 H21 N3 O5
TVQYRIKRPWLBEA-QPJJXVBHSA-N
 Ligand Interaction
SO4
Query on SO4

Download CCD File 
A, B
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
 Ligand Interaction
ZN
Query on ZN

Download CCD File 
A
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
 Ligand Interaction
CL
Query on CL

Download CCD File 
A, B
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
 Ligand Interaction
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.11 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.221 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 65.919α = 90
b = 87.77β = 90
c = 241.831γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
xia2data reduction
AutoPROCdata scaling
PHENIXphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
The Francis Crick InstituteUnited Kingdom--

Revision History 

  • Version 1.0: 2019-11-27
    Type: Initial release
  • Version 1.1: 2019-12-18
    Changes: Database references
  • Version 1.2: 2020-01-29
    Changes: Database references