Unusual phyletic distribution of peptidases as a tool for identifying potential drug targets.
Eukaryote homologues of carboxypeptidases Taq have been discovered by Niemirowicz et al. in the protozoan Trypanosoma cruzi, the causative agent of Chagas' disease. This is surprising, because the peptidase family was thought to be restricted to bacteria and archaea. In this issue of the Biochemical Journal, the authors propose that the Trypanosoma carboxypeptidases are potential drug targets for treatment of the disease. The authors also propose that the presence of the genes in the zooflagellates can be explained by a horizontal transfer of an ancestral gene from a prokaryote. Because peptidases are popular drug targets, identifying parasite or pathogen peptidases that have no homologues in their hosts would be a method to select the most promising targets. To understand how unusual this phyletic distribution is among the 183 families of peptidases, several other examples of horizontal transfers are presented, as well as some unusual losses of peptidase genes.
Rawlings
Neil D
ND
The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
D000818:Animals; D002268:Carboxypeptidases / Q000235:genetics; D016503:Drug Delivery Systems / Q000379:methods; D022761:Gene Transfer, Horizontal; D010447:Peptide Hydrolases / Q000235:genetics*; D014349:Trypanosoma cruzi / Q000201:enzymology* / Q000235:genetics
D002268:Carboxypeptidases; D010447:Peptide Hydrolases