Two crystal structures of dihydrofolate reductase‐thymidylate synthase from Cryptosporidium hominis reveal protein–ligand interactions including a structural basis for observed antifolate resistance
Cryptosporidium hominis is a protozoan parasite that causes acute gastrointestinal illness. There are no effective therapies for cryptosporidiosis, highlighting the need for new drug‐lead discovery. An analysis of the protein–ligand interactions in two crystal structures of dihydrofolate reductase‐thymidylate synthase (DHFR‐TS) from C. hominis, determined at 2.8 and 2.87 Å resolution, reveals that the interactions of residues Ile29, Thr58 and Cys113 in the active site of C. hominis DHFR provide a possible structural basis for the observed antifolate resistance. A comparison with the structure of human DHFR reveals active‐site differences that may be exploited for the design of species‐selective inhibitors.
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