학술논문
X-ray crystal structure and specificity of the Toxoplasma gondii ME49 TgAPN2.
Document Type
Article
Author
Source
Subject
*TOXOPLASMA gondii
*CRYSTAL structure
*PARASITIC diseases
*ANTIPARASITIC agents
*X-rays
*STRUCTURE-activity relationships
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Language
ISSN
0264-6021
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. [ABSTRACT FROM AUTHOR]