Metal ion and inter-domain interactions as functional networks in E. coli topoisomerase I.
Metal ion and inter-domain interactions as functional networks in E. coli topoisomerase I.
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DOI：
10.1016/j.gene.2013.04.008
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发表时间：
2013-07-25
期刊：
影响因子：
3.5
通讯作者：
Palumbo M
中科院分区：
文献类型：
--
作者：
Sissi C;Cheng B;Lombardo V;Tse-Dinh YC;Palumbo M
大肠杆菌拓扑异构酶 I (EcTopoI) 是一种 IA 型细菌拓扑异构酶，由于其作为抗菌治疗新靶点的潜在应用而受到广泛关注。然而，在某种程度上缺乏对其分子水平作用机制的详细了解。这部分是由于酶催化循环的正常进行需要多种因素（金属离子、核酸）。此外，它们中的每一个都会对蛋白质结构产生不同的影响。在这里，我们通过监测 EcTopoI 的催化和结构特性来评估不同成分（DNA、金属离子、蛋白质结构域）在动态环境（如溶液中）中的作用。我们的结果清楚地表明这些组件之间的相互作用在功能上相关，并强调了它们的相互参与。与同一家族的其他酶出现了一些相似之处（例如 DNA 阻止二价金属离子在非选择性结合位点配位）。有趣的是，相同的相互作用（C 端和 N 端结构域相互作用）似乎是这种细菌拓扑异构酶所特有的，这表明它们可以有利地用于设计此类酶的选择性抑制剂。
Escherichia coli Topoisomerase I (EcTopoI) is a type IA bacterial topoisomerase which is receiving large attention due to its potential application as novel target for antibacterial therapeutics. Nevertheless, a detailed knowledge of its mechanism of action at molecular level is to some extent lacking. This is partly due to the requirement of several factors (metal ions, nucleic acid) to the proper progress of the enzyme catalytic cycle. Additionally, each of them can differently affect the protein structure. Here we assess the role of the different components (DNA, metal ions, protein domains) in a dynamic environment as in solution by monitoring the catalytic as well as the structural properties of EcTopoI. Our results clearly indicated the interaction among these components as functionally relevant and underlined their mutual involvement. Some similarities with other enzymes of the same family emerged (for example DNA prevents divalent metal ions coordination at non selective binding sites). Interestingly, same interactions (C- and N- terminal domains interaction) appear to be peculiar of this bacterial topoisomerase which suggest they could be favorable exploited to the design of selective inhibitors for this class of enzyme.
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影响因子：
14.9
作者：
Sissi C;Palumbo M
通讯作者：
Palumbo M
DOI：
10.1006/bbrc.1998.9500
发表时间：
1998-10-20
影响因子：
3.1
作者：
Ahumada, A;Tse-Dinh, YC
通讯作者：
Tse-Dinh, YC
DOI：
10.1039/c003759a
发表时间：
2010-07
期刊：
Metallomics : integrated biometal science
影响因子：
--
作者：
Deweese JE;Osheroff N
通讯作者：
Osheroff N
影响因子：
--
作者：
Annamalai T;Dani N;Cheng B;Tse-Dinh YC
通讯作者：
Tse-Dinh YC
影响因子：
14.9
作者：
Tse-Dinh YC
通讯作者：
Tse-Dinh YC