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Prp8 intein in fungal pathogens: target for potential antifungal drugs

Xiang-Qin Liu1, Jing Yang

  • 1Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, NS, Canada B3H 4H7. pxqliu@dal.ca

FEBS Letters
|August 12, 2004
PubMed

Insights

Inteins within fungal pathogens like Aspergillus and Cryptococcus are identified as potential drug targets. These self-splicing protein sequences in the essential Prp8 protein can be targeted for new antifungal therapies.

Area of Science:

  • Molecular Biology
  • Mycology
  • Drug Discovery

Background:

  • Inteins are protein sequences that catalyze their own removal (splicing).
  • Inteins in pathogenic organisms represent potential targets for antimicrobial drug development.
  • The Prp8 protein is essential and highly conserved across many organisms.

Purpose of the Study:

  • To identify and characterize inteins in key fungal pathogens.
  • To investigate the potential of these inteins as antifungal drug targets.

Main Methods:

  • Bioinformatic analysis to identify inteins in fungal genomes.
  • Recombinant protein expression in Escherichia coli to demonstrate intein splicing activity.
  • Comparative analysis of intein size and domain composition.

Main Results:

  • Inteins were identified within the essential Prp8 protein of Aspergillus fumigatus, Aspergillus nidulans, Histoplasma capsulatum, and Cryptococcus neoformans.
  • Prp8 intein size varied significantly (170–819 amino acids) due to differences in endonuclease and tongs subdomain presence.
  • Demonstrated protein splicing activity of these fungal Prp8 inteins in a heterologous bacterial system.

Conclusions:

  • Fungal Prp8 inteins are viable targets for antifungal drug discovery.
  • The variability in intein structure offers opportunities for targeted drug design.
  • Existing screening and selection methods can be applied to identify drugs targeting these inteins.

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