1XDN

High resolution crystal structure of an editosome enzyme from trypanosoma brucei: RNA editing ligase 1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.20 Å
  • R-Value Free: 0.148 
  • R-Value Work: 0.128 
  • R-Value Observed: 0.129 

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This is version 1.3 of the entry. See complete history


Literature

High resolution crystal structure of a key editosome enzyme from Trypanosoma brucei: RNA editing ligase 1.

Deng, J.Schnaufer, A.Salavati, R.Stuart, K.D.Hol, W.G.

(2004) J Mol Biol 343: 601-613

  • DOI: https://doi.org/10.1016/j.jmb.2004.08.041
  • Primary Citation of Related Structures:  
    1XDN

  • PubMed Abstract: 

    Trypanosomatids are causative agents of several devastating tropical diseases such as African sleeping sickness, Chagas' disease and leishmaniasis. There are no effective vaccines available to date for treatment of these protozoan diseases, while current drugs have limited efficacy, significant toxicity and suffer from increasing resistance. Trypanosomatids have several remarkable and unique metabolic and structural features that are of great interest for developing new anti-protozoan therapeutics. One such feature is "RNA editing", an essential process in these pathogenic protozoa. Transcripts for key trypanosomatid mitochondrial proteins undergo extensive post-transcriptional RNA editing by specifically inserting or deleting uridylates from pre-mature mRNA in order to create mature mRNAs that encode functional proteins. The RNA editing process is carried out in a approximately 1.6 MDa multi-protein complex, the editosome. In Trypanosoma brucei, one of the editosome's core enzymes, the RNA editing ligase 1 (TbREL1), has been shown to be essential for survival of both insect and bloodstream forms of the parasite. We report here the crystal structure of the catalytic domain of TbREL1 at 1.2 A resolution, in complex with ATP and magnesium. The magnesium ion interacts with the beta and gamma-phosphate groups and is almost perfectly octahedrally coordinated by six phosphate and water oxygen atoms. ATP makes extensive direct and indirect interactions with the ligase via essentially all its atoms while extending its base into a deep pocket. In addition, the ATP makes numerous interactions with residues that are conserved in the editing ligases only. Further away from the active site, TbREL1 contains a unique loop containing several hydrophobic residues that are highly conserved among trypanosomatid RNA editing ligases which may play a role in protein-protein interactions in the editosome. The distinct characteristics of the adenine-binding pocket, and the absence of any close homolog in the human genome, bode well for the design of selective inhibitors that will block the essential RNA ligase function in a number of major protozoan pathogens.


  • Organizational Affiliation

    Howard Hughes Medical Institute, University of Washington, Seattle WA 98195, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
RNA editing ligase MP52277Trypanosoma bruceiMutation(s): 3 
Gene Names: MP52
UniProt
Find proteins for P86927 (Trypanosoma brucei brucei (strain 927/4 GUTat10.1))
Explore P86927 
Go to UniProtKB:  P86927
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP86927
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ATP
Query on ATP

Download Ideal Coordinates CCD File 
C [auth A]ADENOSINE-5'-TRIPHOSPHATE
C10 H16 N5 O13 P3
ZKHQWZAMYRWXGA-KQYNXXCUSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
B [auth A]MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
MSE
Query on MSE
A
L-PEPTIDE LINKINGC5 H11 N O2 SeMET
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.20 Å
  • R-Value Free: 0.148 
  • R-Value Work: 0.128 
  • R-Value Observed: 0.129 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 44.911α = 90
b = 58.579β = 100.23
c = 52.984γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data reduction
SCALEPACKdata scaling
SOLVEphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-12-07
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2014-09-10
    Changes: Database references