TMSB4_Molecular Dynamics Studies of Trypanosoma cruzi Trans Sialidase rangeli Sialidase Mutants at the Covalent Intermediate Stage.

DIEGO JAVIER ALONSO DE ARMIÑO; JOSÉ OSVALDO GUY LEZAMA; DARÍO ESTRIN; R. M. S. ALVAREZ; ADRIAN E. ROITBERG

Villa Carlos Paz - Cordoba

Congreso; XLII Reunion anual de la sociedad Argentina de biofisica; 2013

Sociedad Argentina de Biofisica - Universidad Nacional de Córdoba

Trypanosoma cruzi is the causative agent of Chagas´ disease. T. cruzi trans-sialidase (TcTS) was shown to be an important factor in the microorganism´s virulence, and has been proposed as a target for drug design, a goal that requires a thorough understanding of the enzyme´s mechanism. Evidence indicates that the catalytic mechanism involves a long-lived covalent intermediate (CI), which is later attacked by an acceptor glycoconjugate, completing the sialic acid transfer. A key question is thus, how does TcTS protect the CI from hydrolysis until the acceptor glycoconjugate can position itself in the active site for the transfer reaction to take place. Previous works suggested the existence of a new switch mechanism sensitive to lactose, which deactivates the enzyme in abscence of acceptor ligand at the CI stage. Here we present new in silico studies in which we discuss the structural and sequence differences between TcTS and TrSA responsible for it.