Open AccessCrystallization and preliminary crystallographic studies of dihydrofolate reductase‐thymidylate synthase from Trypanosoma cruzi , the Chagas disease pathogen
Author(s) -
Chitnumsub Penchit,
Yuvaniyama Jirundon,
Chahomchuen Thippayarat,
Vilaivan Tirayut,
Yuthavong Yongyuth
Publication year - 2009
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
ISSN - 1744-3091
DOI - 10.1107/s1744309109041979
Subject(s) - thymidylate synthase , dihydrofolate reductase , trypanosoma cruzi , stereochemistry , molecule , crystal structure , transferase , crystallography , enzyme , chemistry , biology , biochemistry , organic chemistry , parasite hosting , fluorouracil , genetics , chemotherapy , world wide web , computer science
Trypanosoma cruzi dihydrofolate reductase‐thymidylate synthase (TcDHFR‐TS) was crystallized in complexes with the dihydrotriazine‐based or quinazoline‐based antifolates C‐448, cycloguanil (CYC) and Q‐8 in order to gain insight into the interactions of this DHFR enzyme with classical and novel inhibitors. The TcDHFR‐TS–C‐448–NDP–dUMP crystal belonged to space group C 222 1 with two molecules per asymmetric unit and diffracted to 2.37 Å resolution. The TcDHFR‐TS–CYC, TcDHFR‐TS–CYC–NDP and TcDHFR‐TS–Q‐8–NDP crystals belonged to space group P 2 1 with four molecules per asymmetric unit and diffracted to 2.1, 2.6 and 2.8 Å resolution, respectively. Crystals belonging to the two different space groups were suitable for structure determination.