2WE6

Crystal Structure of Plasmodium falciparum Ubiquitin Carboxyl- terminal Hydrolase 3 (UCHL3)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.42 Å
  • R-Value Free: 0.251 
  • R-Value Work: 0.218 
  • R-Value Observed: 0.219 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Characterization and Structural Studies of the Plasmodium Falciparum Ubiquitin and Nedd8 Hydrolase Uchl3.

Artavanis-Tsakonas, K.Weihofen, W.A.Antos, J.M.Coleman, B.I.Comeaux, C.A.Duraisingh, M.T.Gaudet, R.Ploegh, H.L.

(2010) J Biol Chem 285: 6857

  • DOI: https://doi.org/10.1074/jbc.M109.072405
  • Primary Citation of Related Structures:  
    2WDT, 2WE6

  • PubMed Abstract: 

    Like their human hosts, Plasmodium falciparum parasites rely on the ubiquitin-proteasome system for survival. We previously identified PfUCHL3, a deubiquitinating enzyme, and here we characterize its activity and changes in active site architecture upon binding to ubiquitin. We find strong evidence that PfUCHL3 is essential to parasite survival. The crystal structures of both PfUCHL3 alone and in complex with the ubiquitin-based suicide substrate UbVME suggest a rather rigid active site crossover loop that likely plays a role in restricting the size of ubiquitin adduct substrates. Molecular dynamics simulations of the structures and a model of the PfUCHL3-PfNedd8 complex allowed the identification of shared key interactions of ubiquitin and PfNedd8 with PfUCHL3, explaining the dual specificity of this enzyme. Distinct differences observed in ubiquitin binding between PfUCHL3 and its human counterpart make it likely that the parasitic DUB can be selectively targeted while leaving the human enzyme unaffected.


  • Organizational Affiliation

    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
UBIQUITIN CARBOXYL-TERMINAL HYDROLASE L3
A, B
232Plasmodium falciparumMutation(s): 0 
EC: 3.4.19.12
UniProt
Find proteins for Q8IKM8 (Plasmodium falciparum (isolate 3D7))
Explore Q8IKM8 
Go to UniProtKB:  Q8IKM8
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8IKM8
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.42 Å
  • R-Value Free: 0.251 
  • R-Value Work: 0.218 
  • R-Value Observed: 0.219 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 168.343α = 90
b = 44.979β = 121.79
c = 99.534γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-12-29
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2023-12-13
    Changes: Data collection, Database references, Other, Refinement description