Crystallization and preliminary crystallographic studies of dihydrofolate reductase-thymidylate synthase from Trypanosoma cruzi, the Chagas disease pathogen
Crystallization and preliminary crystallographic studies of dihydrofolate reductase-thymidylate synthase from Trypanosoma cruzi, the Chagas disease pathogen
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DOI：
10.1107/s1744309109041979
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发表时间：
2009-11-01
影响因子：
0.9
通讯作者：
Yuthavong, Yongyuth
中科院分区：
文献类型：
--
作者：
Chitnumsub, Penchit;Yuvaniyama, Jirundon;Yuthavong, Yongyuth
研究人员将克氏锥虫二氢叶酸还原酶-胸腺苷酸合成酶（TcDHFR-TS）与基于二氢三嗪或基于喹唑啉的抗叶酸药C-448、环胍（CYC）和Q-8进行结晶，以了解该DHFR酶与经典和新型抑制剂的相互作用。TcDHFR-TS-C-448-NDP-dUMP晶体属于C222(1)空间群，每个不对称单元有两个分子，衍射分辨率为2.37埃。TcDHFR-TS-CYC、TcDHFR-TS-CYC- ndp和TcDHFR-TS-Q-8-NDP晶体属于P2(1)空间群，每个不对称单元有4个分子，衍射分辨率分别为2.1、2.6和2.8埃。属于两个不同空间群的晶体适合于结构测定。
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.