A single NMT is relevant for Toxoplasma gondii lytic cycle

ALONSO AM; TUROWSKI VR; RUIZ DM; ORELO BD; MORESCO JJ; YATES JR; CORVI MM

Paraná, Entre Ríos

Congreso; LIV Reunión Anual de la Sociedad Argentina de Investigación em Bioquímica y Biologia Molecular; 2018

Sociedad Argentina de Investigación em Bioquímica y Biologia Molecular

Toxoplasma gondii is the causative agent of toxoplasmosis. This diseaseaffects almost one third of the world?s population with devastatingeffects. Despite thesignificant progress that has been made in order to develop new compounds totreat toxoplasmosis, the current therapeuticagents frequently used have toxicside effects. As such, scientists are in real need of finding new targets ofintervention.Protein myristoylation isa post- and co-translational modificationthat affects a variety of proteins in many cells including parasites. It iscatalyzed by Nmyristoyltranferase(NMT), a conserved enzyme that has beendescribed to be essential in many protozoan pathogens. However, up to date,thereis scarce information on NMT and the extent of this modification in T. gondii. In this work T. gondii NMT (TgNMT) wasidentified andcharacterized. Structural analyses suggest that there aredifferences between human and T. gondii NMTs, which could be of importance todesignspecific inhibitors. Furthermore, this protein presents NMT activity in vitro, is expressed inboth intra- and extracellular parasites and interactswith predicted TgNMTsubstrates. Additionally, TgNMT activity seems to be important for the lyticcycle. An in silicomyristoylome predicts157 proteins to be targeted by this modificationwith some of them being critical for the life cycle of this parasite. Thisanalysis suggests thatmyristoylation could be regulating calcium homeostasiswhich is critical for T.gondii pathogenesis. Together, these data indicate that TgNMTcouldbe an interesting target of intervention for the treatment of toxoplasmosis.