Ligand requirements for glmS ribozyme self-cleavage

Ligand requirements for glmS ribozyme self-cleavage
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DOI:
10.1016/j.chembiol.2005.09.006
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发表时间:
2005-11-01
影响因子:
--
通讯作者:
Soukup, GA
Soukup, GA
中科院分区:
生物1区
文献类型:
--
作者:
McCarthy, TJ;Plog, MA;Soukup, GA

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天然RNA催化剂(核酶)在生物RNA加工和蛋白质合成中执行必要的反应,其中催化作用是RNA结构单独或与金属离子辅因子组合所固有的。最近发现的glmS核酶是独特的,因为它作为葡萄糖胺-6-磷酸(GlcN 6P)依赖性催化剂发挥作用,被认为能够在某些原核生物中实现氨基糖生物合成的“核糖开关”调节。然而,目前还不清楚GlcN 6P是否作为效应子或辅酶来促进核酶自切割。在此,我们证明了配体是glmS核酶自切割活性的绝对必要条件。此外,催化既需要又依赖于GlcN 6P和相关化合物的胺官能团的酸解离常数(pK(α))。数据表明配体是催化不可或缺的,与GlcN 6P的辅酶作用一致,并说明生物RNA催化的扩展能力。
Natural RNA catalysts (ribozymes) perform essential reactions in biological RNA processing and protein synthesis, whereby catalysis is intrinsic to RNA structure alone or in combination with metal ion cofactors. The recently discovered glmS ribozyme is unique in that it functions as a glucosamine-6-phosphate (GlcN6P)-dependent catalyst believed to enable "riboswitch" regulation of amino-sugar biosynthesis in certain prokaryotes. However, it is unclear whether GlcN6P functions as an effector or coenzyme to promote ribozyme self-cleavage. Herein, we demonstrate that ligand is absolutely requisite for glmS ribozyme self-cleavage activity. Furthermore, catalysis both requires and is dependent upon the acid dissociation constant (pK(a)) of the amine functionality of GlcN6P and related compounds. The data demonstrate that Iigand is integral to catalysis, consistent with a coenzyme role for GlcN6P and illustrating an expanded capacity for biological RNA catalysis.