Nineteen tyrosine auxotrophs of the ciliated protozoan Tetrahymena thermophila have been isolated and biochemically examined. These mutants are defective in the conversion of phenylalanine to tyrosine; this is analogous to the defect that causes phenylketonuria in humans. After nitrosoguanidine mutagenesis and self-fertilization, progeny clones were screened for tyrosine auxotrophy and positive...

Escherichia coli (thyA DeltafolA) mutants are viable and can grow in minimal medium when supplemented with thymidine alone. Here we present evidence from in vivo and in vitro studies that the ydgB gene determines an alternative dihydrofolate reductase that is related to the trypanosomatid pteridine reductases. We propose to rename this gene folM.

The treatment of Human African trypanosomiasis remains a major unmet health need in sub-Saharan Africa. Approaches involving new molecular targets are important; pteridine reductase 1 (PTR1), an enzyme that reduces dihydrobiopterin in Trypanosoma spp., has been identified as a candidate target, and it has been shown previously that substituted pyrrolo[2,3-d]pyrimidines are inhibitors of PTR1 fr...

Pistacia integerrima Stew ex Brandis is a valued medicinal plant used for curing various diseases such as diarrhea, fever, liver disorder, pain, asthma, and inflammation. The aim of this study was the isolation bioactive leishmanicidal agents from methanolic extract. extract led to flavonoids 3,5,7,4/-tetrahydroxy-flavanone (1). isolated compound 1 were tested antileishmanial effect. showed per...

BACKGROUND Currently, there are no effective vaccines against leishmaniasis, and treatment using pentavalent antimonial drugs is occasionally effective and often toxic for patients. The PTR1 enzyme, which causes antifolate drug resistance in Leishmania parasites encoded by gene pteridine reductase 1 (ptr1). Since Leishmania lacks pteridine and folate metabolism, it cannot synthesize the pteridi...

Pteridine reductase 1 (PTR1) is a novel broad spectrum enzyme of pterin and folate metabolism in the protozoan parasite Leishmania. Overexpression of PTR1 confers methotrexate resistance to these protozoa, arising from the enzyme's ability to reduce dihydrofolate and its relative insensitivity to methotrexate. The kinetic mechanism and stereochemical course for the catalyzed reaction confirm PT...