Cochrane Jesse C, Lipchock Sarah V, Strobel Scott A
Department of Molecular Biophysics and Biochemistry, Yale University, 260 Whitney Avenue, New Haven, CT 06520, USA.
Chem Biol. 2007 Jan;14(1):97-105. doi: 10.1016/j.chembiol.2006.12.005. Epub 2006 Dec 28.
The GlmS riboswitch is located in the 5'-untranslated region of the gene encoding glucosamine-6-phosphate (GlcN6P) synthetase. The GlmS riboswitch is a ribozyme with activity triggered by binding of the metabolite GlcN6P. Presented here is the structure of the GlmS ribozyme (2.5 A resolution) with GlcN6P bound in the active site. The GlmS ribozyme adopts a compact double pseudoknot tertiary structure, with two closely packed helical stacks. Recognition of GlcN6P is achieved through coordination of the phosphate moiety by two hydrated magnesium ions as well as specific nucleobase contacts to the GlcN6P sugar ring. Comparison of this activator bound and the previously published apoenzyme complex supports a model in which GlcN6P does not induce a conformational change in the RNA, as is typical of other riboswitches, but instead functions as a catalytic cofactor for the reaction. This demonstrates that RNA, like protein enzymes, can employ the chemical diversity of small molecules to promote catalytic activity.
GlmS核糖开关位于编码6-磷酸葡萄糖胺（GlcN6P）合成酶的基因的5'非翻译区。GlmS核糖开关是一种核酶，其活性由代谢物GlcN6P的结合触发。本文展示了结合有GlcN6P的活性位点的GlmS核酶的结构（分辨率为2.5埃）。GlmS核酶采用紧凑的双假结三级结构，有两个紧密堆积的螺旋堆叠。通过两个水合镁离子对磷酸部分的配位以及与GlcN6P糖环的特定核碱基接触来实现对GlcN6P的识别。这种结合激活剂的结构与之前发表的无酶复合物的比较支持了一种模型，即GlcN6P不像其他核糖开关那样诱导RNA的构象变化，而是作为该反应的催化辅因子发挥作用。这表明RNA与蛋白质酶一样，可以利用小分子的化学多样性来促进催化活性。
