Structure of pteridine reductase (PTR1) fromTrypanosoma brucei
نویسندگان
چکیده
منابع مشابه
Crystallization of recombinant Leishmania major pteridine reductase 1 (PTR1).
The enzyme pteridine reductase (PTR1) has recently been discovered in the protozoan parasite Leishmania and validated as a target for therapeutic intervention. PTR1 is responsible for the salvage of pteridines and also contributes to antifolate drug resistance. Structural analysis, in combination with ongoing biochemical characterization will assist the elucidation of the structure-activity rel...
متن کاملStructure and reactivity of Trypanosoma brucei pteridine reductase: inhibition by the archetypal antifolate methotrexate
The protozoan Trypanosoma brucei has a functional pteridine reductase (TbPTR1), an NADPH-dependent short-chain reductase that participates in the salvage of pterins, which are essential for parasite growth. PTR1 displays broad-spectrum activity with pterins and folates, provides a metabolic bypass for inhibition of the trypanosomatid dihydrofolate reductase and therefore compromises the use of ...
متن کاملStructure-Based Design of Pteridine Reductase Inhibitors Targeting African Sleeping Sickness and the Leishmaniases†
Pteridine reductase (PTR1) is a target for drug development against Trypanosoma and Leishmania species, parasites that cause serious tropical diseases and for which therapies are inadequate. We adopted a structure-based approach to the design of novel PTR1 inhibitors based on three molecular scaffolds. A series of compounds, most newly synthesized, were identified as inhibitors with PTR1-specie...
متن کاملNew approaches to Leishmania chemotherapy: pteridine reductase 1 (PTR1) as a target and modulator of antifolate sensitivity.
Leishmania and other trypanosomatid protozoa require reduced pteridines (pterins and folates) for growth, suggesting that inhibition of these pathways could be targeted for effective chemotherapy. This goal has not yet been realized, indicating that pteridine metabolism may be unusual in this lower eukaryote. We have investigated this possibility using both wild type and laboratory-selected ant...
متن کاملDesign, Synthesis and Biological Evaluation of Novel Inhibitors of Trypanosoma brucei Pteridine Reductase 1
Genetic studies indicate that the enzyme pteridine reductase 1 (PTR1) is essential for the survival of the protozoan parasite Trypanosoma brucei. Herein, we describe the development and optimisation of a novel series of PTR1 inhibitors, based on benzo[d]imidazol-2-amine derivatives. Data are reported on 33 compounds. This series was initially discovered by a virtual screening campaign (J. Med. ...
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ژورنال
عنوان ژورنال: Acta Crystallographica Section A Foundations of Crystallography
سال: 2006
ISSN: 0108-7673
DOI: 10.1107/s0108767306097029