核糖开关(Riboswitches)是结构性RNA元素,它们与特定配体结合,来控制它们所结合的基因的表达。核黄素和相关化合物的输送及合成中所涉及的几个细菌基因由一个与黄素单核苷酸(FMN)结合的核糖开关调控。
Serganov等人报告了与FMN、核黄素和一个抗生素相结合的代谢物传感区域的异乎寻常的结构。这一相对来说比较开放的袋状配体结合区域表明,我们有可能设计基于FMN的抗菌素。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature 458, 233-237 (12 March 2009) | doi:10.1038/nature07642
Coenzyme recognition and gene regulation by a flavin mononucleotide riboswitch
Alexander Serganov1,2, Lili Huang1,2 & Dinshaw J. Patel1
1 Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA
2 These authors contributed equally to this work.
The biosynthesis of several protein cofactors is subject to feedback regulation by riboswitches1, 2, 3. Flavin mononucleotide (FMN)-specific riboswitches4, 5, also known as RFN elements6, direct expression of bacterial genes involved in the biosynthesis and transport of riboflavin (vitamin B2) and related compounds. Here we present the crystal structures of the Fusobacterium nucleatum riboswitch bound to FMN, riboflavin and antibiotic roseoflavin7. The FMN riboswitch structure, centred on an FMN-bound six-stem junction, does not fold by collinear stacking of adjacent helices, typical for folding of large RNAs. Rather, it adopts a butterfly-like scaffold, stapled together by opposingly directed but nearly identically folded peripheral domains. FMN is positioned asymmetrically within the junctional site and is specifically bound to RNA through interactions with the isoalloxazine ring chromophore and direct and Mg2+-mediated contacts with the phosphate moiety. Our structural data, complemented by binding and footprinting experiments, imply a largely pre-folded tertiary RNA architecture and FMN recognition mediated by conformational transitions within the junctional binding pocket. The inherent plasticity of the FMN-binding pocket and the availability of large openings make the riboswitch an attractive target for structure-based design of FMN-like antimicrobial compounds. Our studies also explain the effects of spontaneous and antibiotic-induced deregulatory mutations and provided molecular insights into FMN-based control of gene expression in normal and riboflavin-overproducing bacterial strains.