Crystallization and preliminary crystallographic studies of dihydrofolate reductase-thymidylate synthase from Trypanosoma cruzi, the Chagas disease pathogen.
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.
Chitnumsub
Penchit
P
National Center for Genetic Engineering and Biotechnology, Pathumthani, Thailand. penchit@biotec.or.th
Yuvaniyama
Jirundon
J
Chahomchuen
Thippayarat
T
Vilaivan
Tirayut
T
Yuthavong
Yongyuth
Y
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
D009097:Multienzyme Complexes; D015800:Protozoan Proteins; C056930:thymidylate synthase-dihydrofolate reductase; D013762:Tetrahydrofolate Dehydrogenase; D013940:Thymidylate Synthase