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Molecular characterisation of the FtsK DNA motor and its interaction with topo IV in chromosome segregation

FtsK DNA 马达的分子特征及其与染色体分离中拓扑 IV 的相互作用

基本信息

批准号：
BB/D01882X/1
负责人：
Larry Mark Fisher
金额：
$ 31.97万
依托单位：
St George's, University of London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2006
资助国家：
英国
起止时间：
2006 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FD01882X%2F1
关键词：
Molecular characterisation FtsK DNA motor

项目摘要

FtsK is a multifunctional enzyme with the key role of coupling bacterial chromosome segregation and cell division. It is fixed to the DNA septum, a ring structure separating daughter cells, and functions as an ATP-driven DNA motor to pump chromosomal DNA through the closing septal ring. Moreover, it interacts with topo IV, an enzyme that separates topologically interlocked chromosomes and whose activity is blocked by quinolone drugs. These agents are widely used to treat infections caused by Streptococcus pneumoniae and other Gram-positive pathogens. Quinolones trap a topo IV-DNA complex that is converted into a lethal double stranded DNA break by motor proteins that track on DNA. Despite its fundamental scientific and pharmaceutical importance, little is known about topo IV, its interactions with FtsK and quinolones. By using a soluble truncated FtsK protein that retains the DNA motor activity, we aim to study how pneumococcal FtsK directs and modulates topo IV and its targeting by quinolones. The work will lead to significant advances in our understanding of chromosome segregation and cell division, and how antimicrobial quinolones disrupt these processes. In the longer term, the work should aid the development of more effective antibacterials.

FtsK是一种多功能酶，在耦合细菌染色体分离和细胞分裂中起关键作用。它被固定在DNA隔膜上，一个分隔子细胞的环形结构，作为ATP驱动的DNA马达将染色体DNA泵送通过关闭的隔膜环。此外，它与topo IV相互作用，topo IV是一种分离拓扑连锁染色体的酶，其活性被喹诺酮类药物阻断。这些药物广泛用于治疗肺炎链球菌和其他革兰氏阳性病原体引起的感染。喹诺酮类药物捕获拓扑IV-DNA复合物，该复合物通过跟踪DNA的马达蛋白转化为致命的双链DNA断裂。尽管其基本的科学和制药的重要性，很少有人知道拓扑四，它与FtsK和喹诺酮类药物的相互作用。通过使用一个可溶性截短的FtsK蛋白，保留了DNA运动活性，我们的目的是研究肺炎球菌FtsK如何指导和调节拓扑IV和其靶向喹诺酮类药物。这项工作将导致我们对染色体分离和细胞分裂的理解取得重大进展，以及抗菌喹诺酮类药物如何破坏这些过程。从长远来看，这项工作应该有助于开发更有效的抗菌药物。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Clerocidin selectively modifies the gyrase-DNA gate to induce irreversible and reversible DNA damage.

DOI：
10.1093/nar/gkn539
发表时间：
2008-10
期刊：
Nucleic acids research
影响因子：
14.9
作者：
Pan XS;Dias M;Palumbo M;Fisher LM
通讯作者：
Fisher LM

Breakage-reunion domain of Streptococcus pneumoniae topoisomerase IV: crystal structure of a gram-positive quinolone target.

肺炎链球菌的断裂 - 重新结构域IV：革兰氏阳性喹诺酮靶标的晶体结构。

DOI：
10.1371/journal.pone.0000301
发表时间：
2007-03-21
期刊：
PloS one
影响因子：
3.7
作者：
Laponogov I;Veselkov DA;Sohi MK;Pan XS;Achari A;Yang C;Ferrara JD;Fisher LM;Sanderson MR
通讯作者：
Sanderson MR

The difficult case of crystallization and structure solution for the ParC55 breakage-reunion domain of topoisomerase IV from Streptococcus pneumoniae.