Edman J C, Edman U, Cao M, Lundgren B, Kovacs J A, Santi D V
Hormone Research Institute, University of California, San Francisco 94143-0534.
Proc Natl Acad Sci U S A. 1989 Nov;86(22):8625-9. doi: 10.1073/pnas.86.22.8625.
Pneumocystis carinii dihydrofolate reductase (DHFR; 5,6,7,8-tetrahydrofolate: NADP+ oxidoreductase, EC 1.5.1.3) cDNA sequences have been isolated by their ability to confer trimethoprim resistance to Escherichia coli. Consistent with the recent conclusion that P. carinii is a member of the Fungi, sequence analysis and chromosomal localization show that DHFR is neither physically nor genetically linked to thymidylate synthase. Expression of recombinant P. carinii DHFR in heterologous hosts provides an abundant source of the enzyme that may form a basis for the development of new therapies for this enigmatic pathogen. Studies with the recombinant enzyme show that trimethoprim is a very poor inhibitor of P. carinii DHFR and, in fact, is a more potent inhibitor of human DHFR.
卡氏肺孢子虫二氢叶酸还原酶（DHFR；5,6,7,8 - 四氢叶酸：NADP +氧化还原酶，EC 1.5.1.3）的cDNA序列已通过其赋予大肠杆菌甲氧苄啶抗性的能力被分离出来。与最近认为卡氏肺孢子虫是真菌成员的结论一致，序列分析和染色体定位表明，DHFR在物理上和遗传上均与胸苷酸合成酶没有联系。重组卡氏肺孢子虫DHFR在异源宿主中的表达提供了丰富的酶来源，这可能为开发针对这种神秘病原体的新疗法奠定基础。对重组酶的研究表明，甲氧苄啶是卡氏肺孢子虫DHFR的一种非常弱的抑制剂，实际上，它对人DHFR的抑制作用更强。
