X-ray crystal structure and specificity of the Toxoplasma gondii ME49 TgAPN2.

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.

• Authors: Emilia M Marijanovic, Karolina Weronika Swiderska, James Andersen, Jasmin C Aschenbrenner, Chaille T Webb, Marcin Drag, Nyssa Drinkwater, Sheena McGowan
• Journal: The Biochemical journal (Biochem J) Vol. 477 Issue 19 Pg. 3819-3832 (10 16 2020) ISSN: 1470-8728 [Electronic] England
• PMID: 32926129 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Author(s).

Chemical References

• Protozoan Proteins
• Aminopeptidases

Topics

• Aminopeptidases (chemistry)
• Crystallography, X-Ray
• Protozoan Proteins (chemistry)
• Toxoplasma (enzymology)