Sheldon R, Brenner S
Mol Gen Genet. 1976 Aug 10;147(1):91-7. doi: 10.1007/BF00337941.
Trimethoprim inhibits dihydrofolate reductase. Mutations conferring trimethorpim-resistance on E coli K12 result in either an altered reductase with decreased affinity for the drug, or in 2-30 fold higher levels of the enzyme. Studies of the latter class of mutants indicate that dihydrofolate reductase is regulatdd by a diffusible molecule, and is probably under negative control. The regulatrory mutants, some of which are temperature-sensitive, act cis.
甲氧苄啶抑制二氢叶酸还原酶。赋予大肠杆菌K12对甲氧苄啶抗性的突变会导致还原酶发生改变，使其对该药物的亲和力降低，或者使该酶的水平提高2至30倍。对后一类突变体的研究表明，二氢叶酸还原酶受一种可扩散分子的调节，可能处于负调控之下。这些调节突变体中的一些对温度敏感，呈顺式作用。
