A unique RNA fold in the RumA-RNA-Cofactor ternary complex contributes to substrate selectivity and enzymatic function
A unique RNA fold in the RumA-RNA-Cofactor ternary complex contributes to substrate selectivity and enzymatic function
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DOI：
10.1016/j.cell.2004.12.037
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发表时间：
2005-03-11
期刊：
影响因子：
64.5
通讯作者：
Stroud, RM
中科院分区：
文献类型：
--
作者：
Lee, TT;Agarwalla, S;Stroud, RM
在E.大肠杆菌23 S核糖体RNA被其专用酶鲁马甲基化。鲁马/RNA/S-腺苷高半胱氨酸的结构揭示了实现独特选择性的机制。单链底物在酶上“重新折叠”成具有六种关键RNA内相互作用的紧凑构象。RNA底物直接参与催化作用。除了靶碱基之外，第二个碱基从核心环“翻转”以堆叠辅因子S-腺苷高半胱氨酸的腺嘌呤。排列序列顺序的核苷酸堆叠到由翻转的靶U1939空出的位点中，并补偿碱基翻转的能量损失。RNA的3'发夹片段结合活性位点的远端并提供有助于增强催化效率的结合能。RNA在催化中的积极合作使我们得出结论，鲁马及其底物RNA可能反映了最早的RNA-蛋白质时代的特征。
A single base (U1939) within E. coli 23S ribosomal RNA is methylated by its dedicated enzyme, RumA. The structure of RumA/RNA/S-adenosylhomocysteine uncovers the mechanism for achieving unique selectivity. The single-stranded substrate is "refolded" on the enzyme into a compact conformation with six key intra-RNA interactions. The RNA substrate contributes directly to catalysis. In addition to the target base, a second base is "flipped out" from the core loop to stack against the adenine of the cofactor S-adenosylhomocysteine. Nucleotides in permuted sequence order are stacked into the site vacated by the everted target U1939 and compensate for the energetic penalty of base eversion. The 3' hairpin segment of the RNA binds distal to the active site and provides binding energy that contributes to enhanced catalytic efficiency. Active collaboration of RNA in catalysis leads us to conclude that RumA and its substrate RNA may reflect features from the earliest RNA-protein era.