COMP 198 |
| Trypanosoma cruzi trans-sialidase (TcTS) catalyzes the transfer of α-2,3-linked sialic acid to acceptors containing terminal β-galactosyl residues with retention of the anomeric configuration. Via this process, the parasite that causes Chagas' disease—a lethal, chronic disease—is able to escape from the immune system of the host. For the reaction, a Tyr/Glu couple is proposed to act as a nucleophile and form a covalent intermediate by several experimental studies. Molecular dynamics simulations of liganded and unliganded TcTS as well as the covalent intermediate are performed and analyzed for significant enzyme-ligand interactions and differences upon binding. A comparative study is done by using the same approach to Trypanosoma rangeli sialidase (TrSA) which can only catalyze hydrolysis despite its distinct structural similarity to TcTS. This study aims to guide drug-design efforts for TcTS. |
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Molecular Mechanics
8:30 AM-12:05 PM, Tuesday, August 21, 2007 BCEC -- 161, Oral
Division of Computers in Chemistry |