Limited proteolysis of the bifunctional thymidylate synthase-dihydrofolate reductase from Leishmania tropica.
نویسندگان
چکیده
منابع مشابه
Overproduction of a bifunctional thymidylate synthetase-dihydrofolate reductase and DNA amplification in methotrexate-resistant Leishmania tropica.
Leishmania tropica promastigotes that are highly resistant to methotrexate, a dihydrofolate reductase inhibitor, have been developed. Organisms resistant to 1 mM methotrexate have a 40-fold increase in dihydrofolate reductase which is associated with thymidylate synthetase, and they contain amplified regions of DNA that may be directly visualized on stained gels of restriction digests. The ampl...
متن کاملPrimary structure of the gene encoding the bifunctional dihydrofolate reductase-thymidylate synthase of Leishmania major.
We have determined the nucleotide sequence of the dihydrofolate reductase-thymidylate synthetase (DHFR-TS) gene of the protozoan parasite Leishmania major (dihydrofolate reductase, EC 1.5.1.3 and thymidylate synthase, EC 2.1.1.45). The DHFR-TS protein is encoded by a single 1560-base-pair open reading frame within genomic DNA, in contrast to vertebrate DHFRs or mouse and phage T4 TSs, which con...
متن کاملConstruction of a homodimeric dihydrofolate reductase-thymidylate synthase bifunctional enzyme.
A gene encoding a bifunctional homodimeric dihydrofolate reductase-thymidylate synthase (DHFR-TS) was constructed by destroying the stop codon of Escherichia coli dihydrofolate reductase (DHFR) and joining the coding sequences of the monofunctional enzymes by a five amino acid linker. The protein was designed to mimic features of active site proximity and electrostatics in the protozoan DHFR-TS...
متن کاملBiochemical characterization of the bifunctional enzyme dihydrofolate reductase-thymidylate synthase from Leishmania (Viannia) and its evaluation as a drug target.
INTRODUCTION Dihydrofolate reductase (DHFR) has been used successfully as a drug target in the area of anti-bacterial, anti-cancer and anti-malarial therapy. Although this bifunctional enzyme is also a potential drug target for treatment of leishmaniasis, there have been no reports on its efficacy against Leishmania (Viannia) species. MATERIALS AND METHODS The gene encoding the bifunctional D...
متن کاملStructure, genomic organization and transcription of the bifunctional dihydrofolate reductase-thymidylate synthase gene from Crithidia fasciculata.
The bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS) gene from the monogenetic kinetoplastid protozoan, Crithidia fasciculata, was isolated and characterized. The gene is located on a single chromosome of approximately one megabase, and shows significant sequence similarity to other eukaryotic and prokaryotic DHFR and TS genes. There is a single low-abundance polyadenylated D...
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ژورنال
عنوان ژورنال: Proceedings of the National Academy of Sciences
سال: 1985
ISSN: 0027-8424,1091-6490
DOI: 10.1073/pnas.82.21.7188