Dissecting the essential roles of PTR1
نویسندگان
چکیده
BRUCEI AND LEISHMANIA MAJOR Han B. Ong, Natasha Sienkiewicz, Susan Wyllie and Alan H. Fairlamb From the Division of Biological Chemistry & Drug Discovery, College of Life Sciences, University of Dundee, Wellcome Trust Biocentre, Dundee, Scotland DD1 5EH, UK Running title: Essential role of T. brucei PTR1 in recycling dihydropterins Adress correspondence to Professor Alan H. Fairlamb, Division of Biological Chemistry & Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK. Fax: (44)1382385542; Email [email protected]
منابع مشابه
The roles of pteridine reductase 1 and dihydrofolate reductase-thymidylate synthase in pteridine metabolism in the protozoan parasite Leishmania major.
Trypanosomatid protozoans depend upon exogenous sources of pteridines (pterins or folates) for growth. A broad spectrum pteridine reductase (PTR1) was recently identified in Leishmania major, whose sequence places it in the short chain alcohol dehydrogenase protein family although its enzymatic activities resemble dihydrofolate reductases. The properties of PTR1 suggested a role in essential pt...
متن کاملMolecular Cloning, Expression and Enzymatic Assay of Pteridine Reductase 1 from Iranian Lizard Leishmania
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 pterid...
متن کاملMolecular cloning, expression and enzymatic assay of pteridine reductase 1 from Iranian lizard Leishmania.
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...
متن کاملBiochemical and Genetic Tests for Inhibitors of Leishmania Pteridine Pathways
The study of antifolate-resistant mutants of the protozoan parasite Leishmania has provided useful information about genetic processes such as gene amplification and mutation and knowledge of the unique features of the pteridine metabolic pathway in this primitive eukaryote. The novel bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS) is an essential enzyme, yet most DHFR-TS in...
متن کاملTrypanosoma brucei pteridine reductase 1 is essential for survival in vitro and for virulence in mice
Gene knockout and knockdown methods were used to examine essentiality of pteridine reductase (PTR1) in pterin metabolism in the African trypanosome. Attempts to generate PTR1 null mutants in bloodstream form Trypanosoma brucei proved unsuccessful; despite integration of drug selectable markers at the target locus, the gene for PTR1 was either retained at the same locus or elsewhere in the genom...
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