Recognition, opening and stabilization of DNA gates by topo IV the chromosome decatenase
染色体十链酶 topo IV 识别、打开和稳定 DNA 门
基本信息
- 批准号:BB/D014484/1
- 负责人:
- 金额:$ 33.71万
- 依托单位:
- 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:
- 关键词:
项目摘要
The enzyme topo IV mediates the untangling of bacterial chromosomes prior to their segregation at cell division. Topo IV crosses one DNA helix through another allowing the separation of topologically interlocked chromosomes. It does this by an unusual mechanism: it makes a transient double-stranded DNA break (often called a 'gate') in one molecule through which the second DNA molecule is passed. Antibacterial quinolone drugs act by stabilising the open DNA gate which interferes with DNA replication causing cell death. Indeed, quinolones are now important drugs for the treatment of pneumonia and other infections caused by Streptococcus pneumoniae and othe Gram-positive pathogens. Despite it scientific interest and medical importance, little is known about the mechanism of topo IV and its drug interactions. In this study, we aim to examine (i)how S. pneumoniae topo IV recognises and opens potential gate sequences in DNA, and (ii) how quinolones stabilize such gates. The work will make use of synthetic and altered versions of a known topo IV gate which we identified on the S. pneumoniae chromosome. We shall also study the binding of mutant topo IV complexes to identify key protein residues that function to contact and open the DNA gate. Progress on topo IV and its DNA gates will advance fundamental understanding of chromosome biology and will aid the future design of more effective quinolones.
拓扑异构酶IV介导细菌染色体在细胞分裂时分离之前的解开。拓扑四交叉一个DNA螺旋通过另一个允许拓扑连锁染色体的分离。它通过一种不寻常的机制做到这一点:它使一个分子中的瞬时双链DNA断裂(通常称为“门”),第二个DNA分子通过。抗菌喹诺酮类药物通过稳定打开的DNA门起作用,该门干扰DNA复制,导致细胞死亡。事实上,喹诺酮类药物现在是治疗肺炎链球菌和其他革兰氏阳性病原体引起的肺炎和其他感染的重要药物。尽管它的科学兴趣和医学重要性,很少有人知道的机制拓扑异构酶IV及其药物相互作用。在这项研究中,我们的目的是研究(i)如何S。pneumoniae topo IV识别并打开DNA中潜在的门序列,以及(ii)喹诺酮类如何稳定这些门。这项工作将利用我们在S上发现的已知拓扑IV门的合成和改变版本。肺炎染色体。我们还将研究突变体拓扑异构酶IV复合物的结合,以确定关键的蛋白质残基,其功能是接触和打开DNA门。拓扑异构酶IV及其DNA门的进展将促进对染色体生物学的基本理解,并将有助于未来设计更有效的喹诺酮类药物。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Functional determinants of gate-DNA selection and cleavage by bacterial type II topoisomerases.
- DOI:10.1093/nar/gkt696
- 发表时间:2013-11
- 期刊:
- 影响因子:14.9
- 作者:Arnoldi E;Pan XS;Fisher LM
- 通讯作者:Fisher LM
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Larry Mark Fisher其他文献
Larry Mark Fisher的其他文献
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{{ truncateString('Larry Mark Fisher', 18)}}的其他基金
Open Access Block Award 2024 - St George's University of London
2024 年开放获取区块奖 - 伦敦圣乔治大学
- 批准号:
EP/Z531819/1 - 财政年份:2024
- 资助金额:
$ 33.71万 - 项目类别:
Research Grant
Open Access Block Award 2023 - St George's University of London
2023 年开放访问区块奖 - 伦敦圣乔治大学
- 批准号:
EP/Y530323/1 - 财政年份:2023
- 资助金额:
$ 33.71万 - 项目类别:
Research Grant
Open Access Block Award 2022 - St George's University of London
2022 年开放获取区块奖 - 伦敦圣乔治大学
- 批准号:
EP/X526344/1 - 财政年份:2022
- 资助金额:
$ 33.71万 - 项目类别:
Research Grant
Understanding DNA transport by topo IV and gyrase to counter antimicrobial resistance
了解拓扑 IV 和旋转酶的 DNA 转运以对抗抗菌药物耐药性
- 批准号:
MR/T000848/1 - 财政年份:2019
- 资助金额:
$ 33.71万 - 项目类别:
Research Grant
Molecular basis of DNA gating by topo IV and gyrase and its inhibition by antimicrobial drugs
拓扑IV和旋转酶DNA门控的分子基础及其抗菌药物的抑制作用
- 批准号:
BB/K010069/1 - 财政年份:2012
- 资助金额:
$ 33.71万 - 项目类别:
Research Grant
Mechanistic and structural analysis of topo IV and gyrase and their targeting by antibacterial quinolones
Topo IV 和旋转酶的机理和结构分析及其抗菌喹诺酮类药物的靶向作用
- 批准号:
BB/H00405X/1 - 财政年份:2009
- 资助金额:
$ 33.71万 - 项目类别:
Research Grant
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
- 批准号:
BB/D01882X/1 - 财政年份:2006
- 资助金额:
$ 33.71万 - 项目类别:
Research Grant
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