Modulation of catalytic function by differential plasticity of the active site: case study of Trypanosoma cruzi trans-sialidase and Trypanosoma rangeli sialidase.

ABSTRACT: trans-Sialidase is an essential enzyme for Trypanosoma cruzi, the causative agent of Chagas' disease, to escape from the host immune system and to invade the host cells. Therefore, T. cruzi trans-sialidase (TcTS) presents a potential and appealing therapeutic target for this lethal disease. The availability of a structurally very similar enzyme with strict hydrolase activity (Trypanosoma rangeli sialidase, TrSA) provides us a unique opportunity to understand the determinants of their structure and catalytic mechanism. In this study, we compare the catalytic cleft plasticity of free (apo) and ligand-bound (holo) forms of the two enzymes using molecular dynamics simulations. We focus on the mouth of the catalytic cleft that is defined by two residues: W312 and Y119 in TcTS and W312 and S119

SUBMITTER: Demir O 

PROVIDER: S-EPMC2713503 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature