Natural variation in the binding pocket of a parasitic flatworm TRPM channel resolves the basis for praziquantel sensitivity.

ABSTRACT: The drug praziquantel (PZQ) is the key clinical therapy for treating schistosomiasis and other infections caused by parasitic flatworms. A schistosome target for PZQ was recently identified- a transient receptor potential ion channel in the melastatin subfamily (TRPM_PZQ)-however, little is known about the properties of TRPM_PZQ in other parasitic flatworms. Here, TRPM_PZQ orthologs were scrutinized from all currently available parasitic flatworm genomes. TRPM_PZQ is present in all parasitic flatworms, and the consensus PZQ binding site was well conserved. Functional profiling of trematode, cestode, and a free-living flatworm TRPM_PZQ ortholog revealed differing sensitives (~300-fold) of these TRPM_PZQ channels toward PZQ, which m

SUBMITTER: Rohr CM 

PROVIDER: S-EPMC9910428 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature