恶性疟原虫二氢叶酸还原酶-胸苷酸合成酶基因的分子克隆与序列分析
Molecular cloning and sequence analysis of the Plasmodium falciparum dihydrofolate reductase-thymidylate synthase gene.
作者信息
Bzik D J, Li W B, Horii T, Inselburg J
机构信息
Department of Microbiology, Dartmouth Medical School, Hanover, NH 03756.
出版信息
Proc Natl Acad Sci U S A. 1987 Dec;84(23):8360-4. doi: 10.1073/pnas.84.23.8360.
Abstract
Genomic DNA clones that coded for the bifunctional dihydrofolate reductase (DHFR) and thymidylate synthase (TS) (DHFR-TS) activities from a pyrimethamine-sensitive strain of Plasmodium falciparum were isolated and sequenced. The deduced DHFR-TS protein contained 608 amino acids (71,682 Da). The coding region for DHFR-TS contained no intervening sequences and had a high A + T content (75%). The DHFR domain, in the amino-terminal portion of the protein, was joined by a 94-amino acid junction sequence to the TS domain in the carboxyl-terminal portion of the protein. The TS domain was more conserved than the DHFR domain and both P. falciparum domains were more homologous to eukaryotic than to prokaryotic forms of the enzymes. Predicted secondary structures of the DHFR and TS domains were nearly identical to the structures identified in other DHFR and TS enzymes.
摘要
从一株对乙胺嘧啶敏感的恶性疟原虫中分离并测序了编码双功能二氢叶酸还原酶（DHFR）和胸苷酸合成酶（TS）（DHFR-TS）活性的基因组DNA克隆。推导的DHFR-TS蛋白含有608个氨基酸（71,682道尔顿）。DHFR-TS的编码区没有内含序列，且A+T含量很高（75%）。位于蛋白质氨基末端部分的DHFR结构域，通过一个94个氨基酸的连接序列与位于蛋白质羧基末端部分的TS结构域相连。TS结构域比DHFR结构域更保守，并且恶性疟原虫的这两个结构域与真核生物的酶形式比与原核生物的酶形式更同源。DHFR和TS结构域的预测二级结构与在其他DHFR和TS酶中鉴定出的结构几乎相同。
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