Structural roles of monovalent cations in the HDV ribozyme
Structural roles of monovalent cations in the HDV ribozyme
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DOI：
10.1016/j.str.2007.01.017
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发表时间：
2007-03-01
期刊：
影响因子：
5.7
通讯作者：
Doudna, Jennifer A.
中科院分区：
文献类型：
--
作者：
Ke, Ailong;Ding, Fang;Doudna, Jennifer A.
丁型肝炎病毒（HDV）核酶通过一般酸碱化学催化病毒RNA自切割，其中涉及活性位点胞苷和至少一种金属离子。一价金属离子支持缓慢催化，并被提议取代RNA中的结构性但不催化的二价金属离子。为了研究一价阳离子在核酶结构和功能中的作用，我们在铊离子（Tl+）存在下测定了前体HDV核酶的晶体结构。两个Tl+离子可以占据先前观察到的位于易裂磷酸盐附近的二价金属离子六水合物结合位点，但很容易被六氨合钴（一种镁六水合物模拟物和有效的反应抑制剂）竞争。有趣的是，第三个T1+离子与核糖2 '-OH亲核试剂和pro-S-p-断裂磷酸氧形成直接的内球接触。我们讨论了HDV核酶机制的单价阳离子结合可能的结构和催化影响。
The hepatitis delta virus (HDV) ribozyme catalyzes viral RNA self-cleavage through general acid-base chemistry in which an active-site cytidine and at least one metal ion are involved. Monovalent metal ions support slow catalysis and were proposed to substitute for structural, but not catalytic, divalent metal ions in the RNA. To investigate the role of monovalent cations in ribozyme structure and function, we determined the crystal structure of the precursor HDV ribozyme in the presence of thallium ions (Tl+). Two Tl+ ions can occupy a previously observed divalent metal ion hexahydrate-binding site located near the scissile phosphate, but are easily competed away by cobalt hexammine, a magnesium hexahydrate mimic and potent reaction inhibitor. Intriguingly, a third Tl+ ion forms direct inner-sphere contacts with the ribose 2'-OH nucleophile and the pro-S-p scissile phosphate oxygen. We discuss possible structural and catalytic implications of monovalent cation binding for the HDV ribozyme mechanism.