OBJECTIVES Praziquantel is the only drug available for the treatment of schistosomiasis and the state of the exhausted drug discovery pipeline is alarming. We restarted investigations on the abandoned antischistosomal Ro 13-3978, an aryl hydantoin discovered in the early 1980s by Hoffmann La-Roche. METHODS Newly transformed schistosomula and adult Schistosoma mansoni were studied in the prese...

N6-Threonylcarbamoyladenosine (t6A) and its derivatives are universally conserved modified nucleosides found at position 37, 3΄ adjacent to the anticodon in tRNAs responsible for ANN codons. These modifications have pleiotropic functions of tRNAs in decoding and protein synthesis. In certain species of bacteria, fungi, plants and protists, t6A is further modified to the cyclic t6A (ct6A) via de...

DNA methylation (5-methylcytosine, 5mC) plays critical biological functions in mammals and plants as a vital epigenetic marker. The Ten-Eleven translocation dioxygenases (TET1, 2, and 3) have been found to oxidize 5mC to 5-hydroxymethylcytosine (5hmC) and then to 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) in mammalian cells. We report herein three mushroom TET homologues from Coprinop...

Emerging data strongly suggest that the oxidation of DNA bases can contribute to genomic instability. Structural changes to DNA, induced by base oxidation, may reduce the fidelity of DNA replication and interfere with sequence-specific DNA-protein interactions. We have examined the structures of a series of pyrimidine deoxynucleoside oxidation damage products in aqueous solution. The modified n...

Individual DNA molecules can be read at single nucleotide precision using nanopores coupled to processive enzymes. Discrimination among the four canonical bases has been achieved, as has discrimination among cytosine, 5-methylcytosine (mC), and 5-hydroxymethylcytosine (hmC). Two additional modified cytosine bases, 5-carboxylcytosine (caC) and 5-formylcytosine (fC), are produced during enzymatic...

5-Methylcytosine (5 mC) is associated with epigenetic gene silencing in mammals and plants. 5 mC is consecutively oxidized to 5-hydroxymethylcytosine (5 hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) by ten-eleven translocation enzymes. We performed binding and structural studies to investigate the molecular basis of the recognition of the 5 mC oxidation derivatives in the context o...