Download MendeleyX-ray crystal structure and specificity of the Toxoplasma gondii ME49 TgAPN2.
Marijanovic, E.M., Weronika Swiderska, K., Andersen, J., Aschenbrenner, J.C., Webb, C.T., Drag, M., Drinkwater, N., McGowan, S.(2020) Biochem J 477: 3819-3832
- PubMed: 32926129
- DOI: https://doi.org/10.1042/BCJ20200569
- Primary Citation of Related Structures:
6OIU - PubMed Abstract:
Toxoplasmosis is a parasitic disease caused by infection with Toxoplasma gondii that currently has few therapeutic options. The M1 aminopeptidase enzymes have been shown to be attractive targets for anti-parasitic agents and/or vaccine candidates, suggesting potential to re-purpose inhibitors between parasite M1 aminopeptidase targets. The M1 aminopeptidase TgAPN2 has been suggested to be a potential new drug target for toxoplasmosis. Here we investigate the structure and function of TgAPN2, a homologue of the antimalarial drug target PfA-M1, and evaluate the capacity to use inhibitors that target PfA-M1 against TgAPN2. The results show that despite a similar overall fold, the TgAPN2 has a unique substrate specificity and inhibition profile. Sequence and structure differences are investigated and show how comparative structure-activity relationships may provide a route to obtaining potent inhibitors of TgAPN2.
Organizational Affiliation:
Biomedicine Discovery Institute, Department of Microbiology, Monash University Clayton, Melbourne, VIC 3800, Australia.
