Exploring novel strategies for AIDS protozoal pathogens: α-helix mimetics targeting a key allosteric protein-protein interaction in C. hominis TS-DHFR.

ABSTRACT: The bifunctional enzyme thymidylate synthase-dihydrofolate reductase (TS-DHFR) from the protozoal parasite Cryptosporidium hominis is a potential molecular target for the design of antiparasitic therapies for AIDS-related opportunistic infections. The enzyme exists as a homodimer with each monomer containing a unique swap domain known as a "crossover helix" that binds in a cleft on the adjacent DHFR active site. This crossover helix is absent in species containing monofunctional forms of DHFR such as human. An in-depth understanding of protein-protein interactions between the crossover helix and adjacent DHFR active site that might modulate enzyme integrity or function would allow for insights into rational design of species-specific allosteric inhibitors. Mutational analysis couple

SUBMITTER: Martucci WE 

PROVIDER: S-EPMC3855065 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature