3F75

Activated Toxoplasma gondii cathepsin L (TgCPL) in complex with its propeptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.99 Å
  • R-Value Free: 0.206 
  • R-Value Work: 0.165 
  • R-Value Observed: 0.167 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Toxoplasma gondii cathepsin L is the primary target of the invasion-inhibitory compound morpholinurea-leucyl-homophenyl-vinyl sulfone phenyl.

Larson, E.T.Parussini, F.Huynh, M.H.Giebel, J.D.Kelley, A.M.Zhang, L.Bogyo, M.Merritt, E.A.Carruthers, V.B.

(2009) J Biol Chem 284: 26839-26850

  • DOI: https://doi.org/10.1074/jbc.M109.003780
  • Primary Citation of Related Structures:  
    3F75

  • PubMed Abstract: 

    The protozoan parasite Toxoplasma gondii relies on post-translational modification, including proteolysis, of proteins required for recognition and invasion of host cells. We have characterized the T. gondii cysteine protease cathepsin L (TgCPL), one of five cathepsins found in the T. gondii genome. We show that TgCPL is the primary target of the compound morpholinurea-leucyl-homophenyl-vinyl sulfone phenyl (LHVS), which was previously shown to inhibit parasite invasion by blocking the release of invasion proteins from microneme secretory organelles. As shown by fluorescently labeled LHVS and TgCPL-specific antibodies, TgCPL is associated with a discrete vesicular structure in the apical region of extracellular parasites but is found in multiple puncta throughout the cytoplasm of intracellular replicating parasites. LHVS fails to label cells lacking TgCPL due to targeted disruption of the TgCPL gene in two different parasite strains. We present a structural model for the inhibition of TgCPL by LHVS based on a 2.0 A resolution crystal structure of TgCPL in complex with its propeptide. We discuss possible roles for TgCPL as a protease involved in the degradation or limited proteolysis of parasite proteins involved in invasion.


  • Organizational Affiliation

    Medical Structural Genomics of Pathogenic Protozoa Consortium, University of Washington, Seattle, Washington 98195-7742, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cathepsin L Protease224Toxoplasma gondii RHMutation(s): 0 
Gene Names: CPL
EC: 3.4.22.15
UniProt
Find proteins for Q6DMN0 (Toxoplasma gondii)
Explore Q6DMN0 
Go to UniProtKB:  Q6DMN0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6DMN0
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Cathepsin L PropeptideB [auth P]106Toxoplasma gondii RHMutation(s): 0 
Gene Names: CPL
EC: 3.4.22.15
UniProt
Find proteins for Q6DMN0 (Toxoplasma gondii)
Explore Q6DMN0 
Go to UniProtKB:  Q6DMN0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6DMN0
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.99 Å
  • R-Value Free: 0.206 
  • R-Value Work: 0.165 
  • R-Value Observed: 0.167 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 65.621α = 90
b = 65.621β = 90
c = 149.772γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
PHASERphasing
REFMACrefinement
PDB_EXTRACTdata extraction
Blu-Icedata collection
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-11-25
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Source and taxonomy, Version format compliance
  • Version 1.2: 2013-07-31
    Changes: Non-polymer description
  • Version 1.3: 2017-10-25
    Changes: Refinement description
  • Version 1.4: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description