A SINGLE NMT IS RELEVANT FOR Toxoplasma gondiiLYTIC CYCLE

ALONSO, ANDRÉS M.; TUROWSKI VALERIA R; RUIZ, DIEGO M.; ORELO, BARBARA D.; MORESCO, JAMES J.; YATES, JOHN R.; CORVI, MARIA M.

Paraná, Entre Ríos

Congreso; LIV Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2018

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

Toxoplasma gondii is the causative agent of toxoplasmosis. This disease affects almost one third of the world?s population with devastatingeffects. Despite the significant progress that has been made in order to develop new compounds to treat toxoplasmosis, the current therapeuticagents frequently used have toxic side effects. As such, scientists are in real need of finding new targets of intervention.Protein myristoylation isa post- and co-translational modification that affects a variety of proteins in many cells including parasites. It is catalyzed by Nmyristoyltranferase(NMT), a conserved enzyme that has been described 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) was identified andcharacterized. Structural analyses suggest that there are differences between human and T. gondii NMTs, which could be of importance to designspecific inhibitors. Furthermore, this protein presents NMT activity in vitro, is expressed in both intra- and extracellular parasites and interactswith predicted TgNMT substrates. Additionally, TgNMT activity seems to be important for the lytic cycle. An in silicomyristoylome predicts157 proteins to be targeted by this modification with some of them being critical for the life cycle of this parasite. This analysis suggests thatmyristoylation could be regulating calcium homeostasis which is critical for T.gondii pathogenesis. Together, these data indicate that TgNMTcould be an interesting target of intervention for the treatment of toxoplasmosis.