Acta Crystallographica Section D 2010-12-01

High-resolution structures of Trypanosoma brucei pteridine reductase ligand complexes inform on the placement of new molecular entities in the active site of a potential drug target.

Alice Dawson, Lindsay B Tulloch, Keri L Barrack, William N Hunter

Index: Acta Crystallogr. D Biol. Crystallogr. 66(Pt 12) , 1334-40, (2010)

Full Text: HTML

Abstract

Pteridine reductase (PTR1) is a potential target for drug development against parasitic Trypanosoma and Leishmania species. These protozoa cause serious diseases for which current therapies are inadequate. High-resolution structures have been determined, using data between 1.6 and 1.1 Å resolution, of T. brucei PTR1 in complex with pemetrexed, trimetrexate, cyromazine and a 2,4-diaminopyrimidine derivative. The structures provide insight into the interactions formed by new molecular entities in the enzyme active site with ligands that represent lead compounds for structure-based inhibitor development and to support early-stage drug discovery.