Fraser R S, Creanor J
Biochem J. 1975 Jun;147(3):401-10. doi: 10.1042/bj1470401.
RNA synthesis in yeast is rapidly inhibited by 8-hydroxyquinoline and the phenazine antibiotic lomofungin (5-formyl-1-methoxycarbonyl-4,6,8-trihydroxyphenazine). It is shown that lomofungin, like 8-hydroxyquinoline, is a chelating agent for bivalent cations. The mechanism of inhibition of RNA synthesis by lomofungin and 8-hydroxyquinoline was investigated in experiments with isolated Escherichia coli RNA polymerase. The results show that both inhibitors are capable of inhibiting polymerase activity solely by chelating the dissociable cations Mn2+ and Mg2+. Evidence is presented which shows that inhibition may occur in the absence of any direct contact between the RNA polymerase or DNA template and the inhibitor. The possibility that inhibition might also occur by chelation of the Zn2+, which is tightly bound to the polymerase, is discussed: it is concluded that lomofungin or 8-hydroxyquinoline is likely to inhibit the enzyme by removal of Mn2+ and Mg2+ before chelating the Zn2+. On the basis of inhibition by chelation of Mn2+ and Mg2+, explanations are proposed for why lomofungin and 8-hydroxyquinoline inhibit synthesis of ribosomal and polydisperse RNA more than that of 5S RNA and tRNA, and for why protein synthesis is not immediately inhibited in the intact yeast cell.
酵母中的RNA合成会被8-羟基喹啉和吩嗪抗生素洛莫真菌素（5-甲酰基-1-甲氧基羰基-4,6,8-三羟基吩嗪）迅速抑制。研究表明，洛莫真菌素与8-羟基喹啉一样，是二价阳离子的螯合剂。在使用分离的大肠杆菌RNA聚合酶进行的实验中，研究了洛莫真菌素和8-羟基喹啉抑制RNA合成的机制。结果表明，这两种抑制剂都能够仅通过螯合可解离的阳离子Mn2+和Mg2+来抑制聚合酶活性。有证据表明，在RNA聚合酶或DNA模板与抑制剂之间不存在任何直接接触的情况下也可能发生抑制作用。文中讨论了通过螯合与聚合酶紧密结合的Zn2+也可能发生抑制作用的可能性：得出的结论是，洛莫真菌素或8-羟基喹啉可能在螯合Zn2+之前通过去除Mn2+和Mg2+来抑制该酶。基于对Mn2+和Mg2+的螯合抑制作用，对洛莫真菌素和8-羟基喹啉为何对核糖体RNA和多分散RNA的合成抑制作用比对5S RNA和tRNA的抑制作用更强，以及为何完整酵母细胞中的蛋白质合成不会立即受到抑制提出了解释。
