克氏锥虫（恰加斯病病原体）二氢叶酸还原酶-胸苷酸合成酶的结晶及初步晶体学研究
Crystallization and preliminary crystallographic studies of dihydrofolate reductase-thymidylate synthase from Trypanosoma cruzi, the Chagas disease pathogen.
作者信息
Chitnumsub Penchit, Yuvaniyama Jirundon, Chahomchuen Thippayarat, Vilaivan Tirayut, Yuthavong Yongyuth
机构信息
National Center for Genetic Engineering and Biotechnology, Pathumthani, Thailand.
出版信息
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009 Nov 1;65(Pt 11):1175-8. doi: 10.1107/S1744309109041979. Epub 2009 Oct 30.
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.
摘要
克氏锥虫二氢叶酸还原酶-胸苷酸合成酶（TcDHFR-TS）与基于二氢三嗪或喹唑啉的抗叶酸药物C-448、环氯胍（CYC）和Q-8形成复合物结晶，以便深入了解这种DHFR酶与经典和新型抑制剂的相互作用。TcDHFR-TS-C-448-NDP-dUMP晶体属于空间群C222(1)，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晶体属于空间群P2(1)，每个不对称单元有四个分子，衍射分辨率分别为2.1、2.6和2.8埃。属于这两个不同空间群的晶体适合进行结构测定。
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