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 homolog 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.
X-ray crystal structure and specificity of the Toxoplasma gondii ME49 TgAPN2
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Emilia M Marijanovic, Karolina Weronika Swiderka, James Andersen, Jasmin C Aschenbrenner, Chaille T Webb, Marcin Drag, Nyssa Drinkwater, Sheena McGowan; X-ray crystal structure and specificity of the Toxoplasma gondii ME49 TgAPN2. Biochem J BCJ20200569. doi: https://doi.org/10.1042/BCJ20200569
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