A strategy devised to isolate a gene coding for a dihydrofolate reductase from Thermus thermophilus DNA delivered only clones harboring instead a gene (the T. thermophilus dehydrogenase [DH(Tt)] gene) coding for a dihydropteridine reductase which displays considerable dihydrofolate reductase activity (about 20% of the activity detected with 6,7-dimethyl-7,8-dihydropterine in the quinonoid form ...

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 o...

Much of the knowledge of pteridine biosynthesis from purines has come from radioactive tracer studies with whole organisms. Reports on the incorporation of the radioactivity of labeled precursors of purines (1) and of uniformly labeled adenine-1% (2) into riboflavin indicated the utilization of purines for riboflavin synthesis. Furthermore, the results of studies (2, 3) with adenine-814C showed...

The structure of Leishmania major pteridine reductase (PTR1) in complex with NADPH and the inhibitor 2,4,6-triaminoquinazoline (TAQ) has been solved in a new crystal form by molecular replacement and refined to 2.6 A resolution. The inhibitor mimics a fragment, the pterin head group, of the archetypal antifolate drug methotrexate (MTX) and exploits similar chemical features to bind in the PTR1 ...

In 1954, Albert (2) suggested that purmes may be biological precursors of pteridine compounds. This suggestion was made as a result of his demonstration that purines can be transformed chemically into pteridines under mild conditions in the presence of glyoxal. The first experimental evidence that the biogenesis of purines and pteridines are biologically related was provided by Weygand and Wald...

Pteridine reductase 1 (PTR1) is an NADPH dependent reductase that catalyzes the reduction of several pterins and folates. The gene encoding this enzyme was originally identified in Leishmania based on its abilty to provide resistance to the drug methotrexate (MTX). The DNA and amno acid sequences are known , and overproducing strains of Escherichia coli are available. PTR1 has been previously s...