Laboratoire de Chimie des Processus Biologiques, CNRS-UMR 8229, Collège De France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France.
Sorbonne Universités, UPMC University, Paris 06, IBPS, UMR8256, Biology of Aging and Adaptation, 7 quai Saint Bernard, 75252 Paris Cedex 05, France.
Nucleic Acids Res. 2018 Feb 16;46(3):1386-1394. doi: 10.1093/nar/gkx1294.
Post-transcriptional base modifications are important to the maturation process of transfer RNAs (tRNAs). Certain modifications are abundant and present at several positions in tRNA as for example the dihydrouridine, a modified base found in the three domains of life. Even though the function of dihydrourine is not well understood, its high content in tRNAs from psychrophilic bacteria or cancer cells obviously emphasizes a central role in cell adaptation. The reduction of uridine to dihydrouridine is catalyzed by a large family of flavoenzymes named dihydrouridine synthases (Dus). Prokaryotes have three Dus (A, B and C) wherein DusB is considered as an ancestral protein from which the two others derived via gene duplications. Here, we unequivocally established the complete substrate specificities of the three Escherichia coli Dus and solved the crystal structure of DusB, enabling for the first time an exhaustive structural comparison between these bacterial flavoenzymes. Based on our results, we propose an evolutionary scenario explaining how substrate specificities has been diversified from a single structural fold.
转录后碱基修饰对于转移 RNA(tRNA) 的成熟过程很重要。某些修饰在 tRNA 中非常丰富，并且存在于多个位置，例如二氢尿嘧啶，这是一种在生命的三个领域中都存在的修饰碱基。尽管二氢尿嘧啶的功能尚未完全理解，但它在嗜冷菌或癌细胞中的 tRNA 中含量很高，显然在细胞适应中起着核心作用。尿嘧啶向二氢尿嘧啶的还原是由一大类名为二氢尿嘧啶合酶(Dus)的黄素酶催化的。原核生物有三种 Dus(A、B 和 C)，其中 DusB 被认为是一种古老的蛋白质，另外两种通过基因复制衍生而来。在这里，我们明确确定了三种大肠杆菌 Dus 的完整底物特异性，并解决了 DusB 的晶体结构，首次能够对这些细菌黄素酶进行详尽的结构比较。基于我们的结果，我们提出了一个进化情景，解释了如何从单一结构折叠中多样化底物特异性。
