PDBsum entry 3ess

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Transferase,toxin PDB id
Protein chain
199 a.a.
Waters ×443
PDB id:
Name: Transferase,toxin
Title: Catalytic fragment of cholix toxin from vibrio cholerae in complex with the 1,8-naphthalimide inhibitor
Structure: Cholix toxin. Chain: a. Fragment: c-terminal catalytic domain (unp residues 459 to 665). Engineered: yes
Source: Vibrio cholerae. Organism_taxid: 666. Strain: tp. Gene: chxa, toxa. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.19Å     R-factor:   0.132     R-free:   0.154
Authors: A.R.Merrill,R.Jorgensen
Key ref: Z.Turgeon et al. (2009). Yeast as a tool for characterizing mono-ADP-ribosyltransferase toxins. FEMS Microbiol Lett, 300, 97. PubMed id: 19793133 DOI: 10.1111/j.1574-6968.2009.01777.x
06-Oct-08     Release date:   15-Sep-09    
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Protein chain
Pfam   ArchSchema ?
Q5EK40  (CHXA_VIBCL) -  Cholix toxin
666 a.a.
199 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     NAD+-diphthamide ADP-ribosyltransferase activity     1 term  


DOI no: 10.1111/j.1574-6968.2009.01777.x FEMS Microbiol Lett 300:97 (2009)
PubMed id: 19793133  
Yeast as a tool for characterizing mono-ADP-ribosyltransferase toxins.
Z.Turgeon, D.White, R.Jørgensen, D.Visschedyk, R.J.Fieldhouse, D.Mangroo, A.R.Merrill.
The emergence of bacterial antibiotic resistance poses a significant challenge in the pursuit of novel therapeutics, making new strategies for drug discovery imperative. We have developed a yeast growth-defect phenotypic screen to help solve this current dilemma. This approach facilitates the identification and characterization of a new diphtheria toxin (DT) group, ADP-ribosyltransferase toxins from pathogenic bacteria. In addition, this assay utilizes Saccharomyces cerevisiae, a reliable model for bacterial toxin expression, to streamline the identification and characterization of new inhibitors against this group of bacterial toxins that may be useful for antimicrobial therapies. We show that a mutant of the elongation factor 2 target protein in yeast, G701R, confers resistance to all DT group toxins and recovers the growth-defect phenotype in yeast. We also demonstrate the ability of a potent small-molecule toxin inhibitor, 1,8-naphthalimide (NAP), to alleviate the growth defect caused by toxin expression in yeast. Moreover, we determined the crystal structure of the NAP inhibitor-toxin complex at near-atomic resolution to provide insight into the inhibitory mechanism. Finally, the NAP inhibitor shows therapeutic protective effects against toxin invasion of mammalian cells, including human lung cells.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21219649 D.Lee, Beer, R.A.Laskowski, J.M.Thornton, and C.A.Orengo (2011).
1,000 structures and more from the MCSG.
  BMC Struct Biol, 11, 2.  
21170356 R.J.Fieldhouse, Z.Turgeon, D.White, and A.R.Merrill (2010).
Cholera- and anthrax-like toxins are among several new ADP-ribosyltransferases.
  PLoS Comput Biol, 6, e1001029.  
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