3CVN

Structure of Peroxisomal Targeting Signal 1 (PTS1) binding domain of Trypanosoma brucei Peroxin 5 (TbPEX5)complexed to T. brucei Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) PTS1 peptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.265 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.196 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Structural Insights into the recognition of peroxisomal targeting signal 1 by Trypanosoma brucei peroxin 5.

Sampathkumar, P.Roach, C.Michels, P.A.Hol, W.G.

(2008) J Mol Biol 381: 867-880

  • DOI: https://doi.org/10.1016/j.jmb.2008.05.089
  • Primary Citation of Related Structures:  
    3CV0, 3CVL, 3CVN, 3CVP, 3CVQ

  • PubMed Abstract: 

    Glycosomes are peroxisome-like organelles essential for trypanosomatid parasites. Glycosome biogenesis is mediated by proteins called "peroxins," which are considered to be promising drug targets in pathogenic Trypanosomatidae. The first step during protein translocation across the glycosomal membrane of peroxisomal targeting signal 1 (PTS1)-harboring proteins is signal recognition by the cytosolic receptor peroxin 5 (PEX5). The C-terminal PTS1 motifs interact with the PTS1 binding domain (P1BD) of PEX5, which is made up of seven tetratricopeptide repeats. Obtaining diffraction-quality crystals of the P1BD of Trypanosoma brucei PEX5 (TbPEX5) required surface entropy reduction mutagenesis. Each of the seven tetratricopeptide repeats appears to have a residue in the alpha(L) conformation in the loop connecting helices A and B. Five crystal structures of the P1BD of TbPEX5 were determined, each in complex with a hepta- or decapeptide corresponding to a natural or nonnatural PTS1 sequence. The PTS1 peptides are bound between the two subdomains of the P1BD. These structures indicate precise recognition of the C-terminal Leu of the PTS1 motif and important interactions between the PTS1 peptide main chain and up to five invariant Asn side chains of PEX5. The TbPEX5 structures reported here reveal a unique hydrophobic pocket in the subdomain interface that might be explored to obtain compounds that prevent relative motions of the subdomains and interfere selectively with PTS1 motif binding or release in trypanosomatids, and would therefore disrupt glycosome biogenesis and prevent parasite growth.


  • Organizational Affiliation

    Department of Biochemistry, Biomolecular Structure Center, University of Washington, Box 357742, Seattle, WA 98195, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Peroxisome targeting signal 1 receptor327Trypanosoma bruceiMutation(s): 2 
Gene Names: PEX5
UniProt
Find proteins for Q9U7C3 (Trypanosoma brucei)
Explore Q9U7C3 
Go to UniProtKB:  Q9U7C3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9U7C3
Sequence Annotations
Expand
  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
T. brucei GAPDH PTS1 peptide Ac-DRDAAKL7Trypanosoma brucei bruceiMutation(s): 0 
UniProt
Find proteins for P22512 (Trypanosoma brucei brucei)
Explore P22512 
Go to UniProtKB:  P22512
Entity Groups  
UniProt GroupP22512
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
EDO
Query on EDO

Download Ideal Coordinates CCD File 
C [auth A]
D [auth A]
E [auth A]
F [auth A]
G [auth A]
C [auth A],
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A],
K [auth A],
L [auth A],
M [auth A],
N [auth A],
O [auth A],
P [auth A],
Q [auth A],
R [auth A],
S [auth A],
T [auth A],
U [auth A],
V [auth A],
W [auth A],
X [auth B]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.265 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.196 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 44.619α = 90
b = 66.178β = 104.55
c = 51.979γ = 90
Software Package:
Software NamePurpose
d*TREKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
StructureStudiodata collection
d*TREKdata reduction
MOLREPphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-06-24
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2018-01-24
    Changes: Structure summary
  • Version 1.3: 2021-10-20
    Changes: Database references, Derived calculations
  • Version 1.4: 2023-08-30
    Changes: Data collection, Refinement description