Mechanistic Characterization of Toxoplasma gondiiThymidylate Synthase (TS-DHFR)-Dihydrofolate Reductase
نویسندگان
چکیده
منابع مشابه
Sequence variation in the dihydrofolate reductase-thymidylate synthase (DHFR-TS) and trypanothione reductase (TR) genes of Trypanosoma cruzi.
Dihydrofolate reductase-thymidylate synthase (DHFR-TS) and trypanothione reductase (TR) are important enzymes for the metabolism of protozoan parasites from the family Trypanosomatidae (e.g. Trypanosoma spp., Leishmania spp.) that are targets of current drug-design studies. Very limited information exists on the levels of genetic polymorphism of these enzymes in natural populations of any trypa...
متن کاملSelection against the dihydrofolate reductase-thymidylate synthase (DHFR-TS) locus as a probe of genetic alterations in Leishmania major.
The genome of the trypanosomatid protozoan genus Leishmania has been shown to undergo a number of changes relevant to drug resistance and virulence, such as gene amplification, chromosomal rearrangement, and variation in ploidy. Experimental approaches to the study of genomic changes have in some cases been limited by the fact that Leishmania cells are asexual diploids, as are some other trypan...
متن کاملTrypanosoma brucei DHFR-TS Revisited: Characterisation of a Bifunctional and Highly Unstable Recombinant Dihydrofolate Reductase-Thymidylate Synthase
Bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS) is a chemically and genetically validated target in African trypanosomes, causative agents of sleeping sickness in humans and nagana in cattle. Here we report the kinetic properties and sensitivity of recombinant enzyme to a range of lipophilic and classical antifolate drugs. The purified recombinant enzyme, expressed as a fusi...
متن کاملDisruption of the crossover helix impairs dihydrofolate reductase activity in the bifunctional enzyme TS-DHFR from Cryptosporidium hominis.
In contrast with most species, including humans, which have monofunctional forms of the folate biosynthetic enzymes TS (thymidylate synthase) and DHFR (dihydrofolate reductase), several pathogenic protozoal parasites, including Cryptosporidium hominis, contain a bifunctional form of the enzymes on a single polypeptide chain having both catalytic activities. The crystal structure of the bifuncti...
متن کاملmolecular characterization of dihydrofolate reductase-thymidylate synthase gene concerning antifulate resistance of plasmodium vivax
background: the recently reported resistance to antimalarials contributes to making the control of malaria more difficult. there is a need to evaluate the current antimalaria regimens to prevent this emerging problem. the aim of this study was to determine dihydrofolate reductase-thymidylate synthase gene mutation ( pvdhfr ) regarding antifulate resistance in plasmodium vivax . methods : from...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 2002
ISSN: 0021-9258
DOI: 10.1074/jbc.m206523200