Open AccessHigh‐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
Author(s) -
Dawson Alice,
Tulloch Lindsay B.,
Barrack Keri L.,
Hunter William N.
Publication year - 2010
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
ISSN - 1399-0047
DOI - 10.1107/s0907444910040886
Subject(s) - trypanosoma brucei , pteridine , active site , drug discovery , dihydrofolate reductase , biology , drug , trypanosoma , antiparasitic , drug development , pharmacology , stereochemistry , biochemistry , computational biology , chemistry , enzyme , medicine , genetics , pathology , gene
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.