Tetramerization and cooperativity in Plasmodium falciparum glutathione S-transferase are mediated by atypic loop 113-119.

ABSTRACT: Glutathione S-transferase of Plasmodium falciparum (PfGST) displays a peculiar dimer to tetramer transition that causes full enzyme inactivation and loss of its ability to sequester parasitotoxic hemin. Furthermore, binding of hemin is modulated by a cooperative mechanism. Site-directed mutagenesis, steady-state kinetic experiments, and fluorescence anisotropy have been used to verify the possible involvement of loop 113-119 in the tetramerization process and in the cooperative phenomenon. This protein segment is one of the most prominent structural differences between PfGST and other GST isoenzymes. Our results demonstrate that truncation, increased rigidity, or even a simple point mutation of this loop causes a dramatic change in the tetramerization kinetics that becomes at least 100 tim

SUBMITTER: Liebau E 

PROVIDER: S-EPMC2755937 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature