First three-dimensional structure of Toxoplasma gondii thymidylate synthase-dihydrofolate reductase: insights for catalysis, interdomain interactions, and substrate channeling.

ABSTRACT: Most species, such as humans, have monofunctional forms of thymidylate synthase (TS) and dihydrofolate reductase (DHFR) that are key folate metabolism enzymes making critical folate components required for DNA synthesis. In contrast, several parasitic protozoa, including Toxoplasma gondii , contain a unique bifunctional thymidylate synthase-dihydrofolate reductase (TS-DHFR) having the catalytic activities contained on a single polypeptide chain. The prevalence of T. gondii infections across the world, especially for those immunocompromised, underscores the need to understand TS-DHFR enzyme function and to find new avenues to exploit for the design of novel antiparasitic drugs. As a first step, we have solved the first three-dimensional structures of T. gondii TS-DHFR at 3.7 Å and of a loop

SUBMITTER: Sharma H 

PROVIDER: S-EPMC3905773 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature