Effects of magnesium and related divalent metal ions in topoisomerase structure and function.
Effects of magnesium and related divalent metal ions in topoisomerase structure and function.
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DOI：
10.1093/nar/gkp024
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发表时间：
2009-02
影响因子：
14.9
通讯作者：
Palumbo M
中科院分区：
文献类型：
--
作者：
Sissi C;Palumbo M
从生物物理和生物化学的角度对DNA拓扑异构酶产生生物学效应的催化步骤以及药物分子对酶-DNA裂解复合体的干扰进行了深入的研究。这提供了关于这一重要酶家族如何在生命系统中工作以及它们的功能如何被天然和合成化合物削弱的基本结构洞察。除了其他因素外，生理环境对拓扑异构酶的生物学性质也有很大的影响，金属离子辅因子，特别是二价离子(Mg2+)，通过利用离子大小、硬度和配位球的特征(包括配位数和几何构型)等独特的化学特征，对赋予和调节催化活性至关重要。事实上，金属离子通过影响正向和反向步骤的动力学以及通过改变酶的构象和灵活性来调节拓扑异构酶驱动的转磷酸化过程的基本方面。对IA型和II型酶特别感兴趣的是涉及Toprim折叠的离子相互作用，Toprim折叠是一个通过进化保守的蛋白质结构域，包含许多催化必不可少的酸性残基。一般的双金属离子机制被广泛接受来解释到目前为止可用的生物物理和生化数据。
The catalytic steps through which DNA topoisomerases produce their biological effects and the interference of drug molecules with the enzyme–DNA cleavage complex have been thoroughly investigated both from the biophysical and the biochemical point of view. This provides the basic structural insight on how this family of essential enzymes works in living systems and how their functions can be impaired by natural and synthetic compounds. Besides other factors, the physiological environment is known to affect substantially the biological properties of topoisomerases, a key role being played by metal ion cofactors, especially divalent ions (Mg2+), that are crucial to bestow and modulate catalytic activity by exploiting distinctive chemical features such as ionic size, hardness and characteristics of the coordination sphere including coordination number and geometry. Indeed, metal ions mediate fundamental aspects of the topoisomerase-driven transphosphorylation process by affecting the kinetics of the forward and the reverse steps and by modifying the enzyme conformation and flexibility. Of particular interest in type IA and type II enzymes are ionic interactions involving the Toprim fold, a protein domain conserved through evolution that contains a number of acidic residues essential for catalysis. A general two-metal ion mechanism is widely accepted to account for the biophysical and biochemical data thus far available.
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影响因子：
16
作者：
Krogh, BO;Shuman, S
通讯作者：
Shuman, S
影响因子：
3
作者：
Andreini, Claudia;Bertini, Ivano;Thornton, Janet M.
通讯作者：
Thornton, Janet M.
影响因子：
64.8
作者：
Dong, Ken C.;Berger, James M.
通讯作者：
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影响因子：
2.9
作者：
Hiasa, H
通讯作者：
Hiasa, H
DOI：
10.1073/pnas.95.14.7876
发表时间：
1998-07-07
影响因子：
11.1
作者：
Berger, JM;Fass, D;Harrison, SC
通讯作者：
Harrison, SC