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PDBsum entry 2wdt

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protein metals Protein-protein interface(s) links
Hydrolase/protein binding PDB id
2wdt
Jmol
Contents
Protein chains
204 a.a. *
76 a.a. *
Metals
_CL ×2
Waters ×189
* Residue conservation analysis
PDB id:
2wdt
Name: Hydrolase/protein binding
Title: Crystal structure of plasmodium falciparum uchl3 in complex with the suicide inhibitor ubvme
Structure: Ubiquitin carboxyl-terminal hydrolase l3. Chain: a, c. Synonym: uchl3, uch-l3, ubiquitin thiolesterase. Engineered: yes. Ubiquitin. Chain: b, d. Fragment: residues 1-75. Engineered: yes. Other_details: c-terminal gly76 of wildtype ubiquitin is re
Source: Plasmodium falciparum. Malaria parasite. Organism_taxid: 5833. Strain: clone 3d7. Expressed in: escherichia coli. Expression_system_taxid: 469008. Homo sapiens. Human. Organism_taxid: 9606.
Resolution:
2.30Å     R-factor:   0.188     R-free:   0.235
Authors: W.A.Weihofen,K.Artavanis-Tsakonas,R.Gaudet,H.L.Ploegh
Key ref: K.Artavanis-Tsakonas et al. (2010). Characterization and structural studies of the Plasmodium falciparum ubiquitin and Nedd8 hydrolase UCHL3. J Biol Chem, 285, 6857-6866. PubMed id: 20042598
Date:
26-Mar-09     Release date:   29-Dec-09    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q8IKM8  (Q8IKM8_PLAF7) -  Ubiquitin carboxyl-terminal hydrolase, putative
Seq:
Struc:
232 a.a.
204 a.a.
Protein chains
No UniProt id for this chain
Struc: 76 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   2 terms 
  Biological process     protein deneddylation   3 terms 
  Biochemical function     hydrolase activity     4 terms  

 

 
J Biol Chem 285:6857-6866 (2010)
PubMed id: 20042598  
 
 
Characterization and structural studies of the Plasmodium falciparum ubiquitin and Nedd8 hydrolase UCHL3.
K.Artavanis-Tsakonas, W.A.Weihofen, J.M.Antos, B.I.Coleman, C.A.Comeaux, M.T.Duraisingh, R.Gaudet, H.L.Ploegh.
 
  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.