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首页> 外文期刊>Biochemistry >Metal Binding Motif in the Active Site of the HDV Ribozyme Binds Divalent and Monovalent Ions
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Metal Binding Motif in the Active Site of the HDV Ribozyme Binds Divalent and Monovalent Ions

机译：HDV核酶活性位点的金属结合基元结合二价和单价离子

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摘要

The hepatitis delta virus (HDV) ribozyme uses both metal ion and nucleobase catalysis in its cleavage mechanism. A reverse G center dot U wobble was observed in a recent crystal structure of the precleaved state. This unusual base pair positions a Mg2+ ion to participate in catalysis. Herein, we used molecular dynamics (MD) and X-ray crystallography to characterize the conformation and metal binding characteristics of this base pair in product and precleaved forms. Beginning with a crystal structure of the product form, we observed formation of the reverse G center dot U wobble during MD trajectories. We also demonstrated that this base pair is compatible with the diffraction data for the product-bound state. During MD trajectories of the product form, Na+ ions interacted with the reverse G center dot U wobble in the RNA active site, and a Mg2+ ion, introduced in certain trajectories, remained bound at this site. Beginning with a crystal structure of the precleaved form, the reverse G center dot U wobble with bound Mg2+ remained intact during MD simulations. When we removed Mg2+ from the starting precleaved structure, Na+ ions interacted with the reverse G center dot U wobble. In support of the computational results, we observed competition between Na+ and Mg2+ in the precleaved ribozyme crystallographically. Nonlinear Poisson-Boltzmann calculations revealed a negatively charged patch near the reverse G center dot U wobble. This anionic pocket likely serves to bind metal ions and to help shift the pK(a) of the catalytic nucleobase, C75. Thus, the reverse G center dot U wobble motif serves to organize two catalytic elements, a metal ion and catalytic nucleobase, within the active site of the HDV ribozyme.
机译：肝炎三角洲病毒（HDV）核酶在裂解机制中同时使用金属离子和核碱基催化。在预裂态的最近晶体结构中观察到反向的G中心点U摆动。这个不寻常的碱基对定位Mg2 +离子参与催化。在这里，我们使用分子动力学（MD）和X射线晶体学来表征该碱基对在产物和预裂解形式中的构象和金属结合特性。从产物形式的晶体结构开始，我们观察到在MD轨迹期间形成了反向G中心点U摆动。我们还证明了该碱基对与产物结合态的衍射数据兼容。在产物形式的MD轨迹期间，Na +离子与RNA活性位点中的反向G中心点U摆动相互作用，并且在某些轨迹中引入的Mg2 +离子仍在该位点结合。从预裂解形式的晶体结构开始，在MD模拟过程中，带有结合的Mg2 +的反向G中心点U摆动保持完整。当我们从起始的预裂解结构中除去Mg2 +时，Na +离子与反向G中心点U摆动相互作用。为了支持计算结果，我们在晶体学上观察到了预先裂解的核酶中Na +和Mg2 +之间的竞争。非线性Poisson-Boltzmann计算显示，在反向G中心点U摆动附近带有负电荷的色块。该阴离子袋可能用于结合金属离子并帮助转移催化核碱基C75的pK（a）。因此，反向G中心点U摆动主题用于在HDV核酶的活性位点内组织两个催化元素，金属离子和催化核碱基。

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