title: Crystallization and preliminary crystallographic studies of dihydrofolate reductase-thymidylate synthase from Trypanosoma cruzi, the Chagas disease pathogen.
abstract: 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 C222(1) with two molecules per asymmetric unit and diffracted to 2.37 angstrom resolution. The TcDHFR-TS-CYC, TcDHFR-TS-CYC-NDP and TcDHFR-TS-Q-8-NDP crystals belonged to space group P2(1) with four molecules per asymmetric unit and diffracted to 2.1, 2.6 and 2.8 angstrom resolution, respectively. Crystals belonging to the two different space groups were suitable for structure determination.
authors.affiliation: National Center for Genetic Engineering and Biotechnology, Pathumthani, Thailand. penchit@biotec.or.th
authors.forename: Penchit
authors.initials: P
authors.lastname: Chitnumsub
authors.forename: Jirundon
authors.initials: J
authors.lastname: Yuvaniyama
authors.forename: Thippayarat
authors.initials: T
authors.lastname: Chahomchuen
authors.forename: Tirayut
authors.initials: T
authors.lastname: Vilaivan
authors.forename: Yongyuth
authors.initials: Y
authors.lastname: Yuthavong
mesh_terms: D014355:Chagas Disease / Q000469:parasitology*; D003460:Crystallization; D018360:Crystallography, X-Ray; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000737:chemistry*; D015800:Protozoan Proteins / Q000737:chemistry; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry*; D013940:Thymidylate Synthase / Q000737:chemistry*; D014349:Trypanosoma cruzi / Q000201:enzymology* / Q000472:pathogenicity
chemical_list: D009097:Multienzyme Complexes; D015800:Protozoan Proteins; C056930:thymidylate synthase-dihydrofolate reductase; D013762:Tetrahydrofolate Dehydrogenase; D013940:Thymidylate Synthase