Application | Comment | Organism |
---|---|---|
medicine | Double knock-out lines of bifunctional dihydrofolate reductase-thymidylate synthase are unable to infect mice, whereas the virulence of single knock-out lines is similar to wild-type | Trypanosoma brucei |
Protein Variants | Comment | Organism |
---|---|---|
additional information | growth of a single knock-out line of bifunctional dihydrofolate reductase-thymidylate synthase is identical to wild-type cells. Double knock-out cells have an absolute requirement for thymidine. Removal of thymidine from the medium triggers growth arrest in S phase, associated with gross morphological changes, followed by cell death after 60 h. Double knock-out lines are unable to infect mice, whereas the virulence of single knock-out lines is similar to wild-type. Double knock-out trypanosomes show reduced sensitivity to trimetrexate or raltitrexed. Pteridine reductase is not able to compensate for loss of dihydrofolate activity | Trypanosoma brucei |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(2S)-2-[(5-{methyl[(2-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)methyl]amino}thiophen-2-yl)formamido]pentanedioic acid | in low-folate medium, up to 300-fold increase of inhibitory activity | Trypanosoma brucei | |
methotrexate | in low-folate medium, up to 300-fold increase of inhibitory activity | Trypanosoma brucei | |
pyrimethamine | no increase in inhibitory activity in low-folate medium | Trypanosoma brucei | |
trimetrexate | no increase in inhibitory activity in low-folate medium | Trypanosoma brucei |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Trypanosoma brucei | - |
bifunctional dihydrofolate reductase-thymidylate synthase | - |