Proton transfer facilitated by ligand binding. An energetic analysis of the catalytic mechanism of Trypanosoma cruzi trans-sialidase.

ABSTRACT: Trans-sialidase is a crucial enzyme for the infection of Trypanosoma cruzi, the protozoa responsible for Chagas' disease in humans. This enzyme catalyzes the transfer of sialic acids from mammalian host cells to parasitic cell surfaces in order to mask the infection from the host's immune system. It represents a promising target for the development of therapeutics to treat the disease and has been subject of extensive structural studies. Elaborate experiments suggested formation of a long-lived covalent intermediate in the catalytic mechanism and identified a Tyr/Glu pair as an unusual catalytic couple. This requires that the tyrosine hydroxyl proton is transferred to the carboxylate group of glutamate before the nucleophilic attack. Since the solution pK(a)s of tyrosine and glutamate are

SUBMITTER: Pierdominici-Sottile G 

PROVIDER: S-EPMC3033446 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature