Mapping C-C nucleoside bond formation in real time
Mapping C-C nucleoside bond formation in real time
批准号:
BB/T006161/1
负责人:
James Naismith
金额:
$57.46万
依托单位国家:
英国
项目类别:
Research Grant
财政年份:
2020
资助国家:
英国
项目状态:
未结题
起止时间:
2020 至 --
中文摘要
我们已经开始研究一种重要的新型酶,它能在两个碳原子之间形成键。碳碳键的形成既是生命最基本的化学,也是酶化学的中心支柱。能够使用一种酶来形成这种键,将使制造新药成为可能。我们的目标是所谓的C-核苷。这些分子诱骗细菌和病毒使用它们,而不是天然的N-核苷。由于使用这些分子,病毒和细菌被杀死。碳碳键是这些分子的绝对关键,它阻止细菌和病毒降解化合物。这些C-核苷是自然界使用的,但它们很难制造,因此需要酶等新方法来制造它们。我们正在研究的系统也很有吸引力,因为我们可以用它来研究实时观看化学的巨大挑战。化学家出现的时间大约是十亿分之一秒,对于大多数技术来说,这是远远不够的,但新的X射线自由电子激光在大约一万亿分之一秒的时间内完成了实验,使我们第一次看到了酶催化的化学反应。这项开创性的实验将需要大量的准备工作和赠款将开发的新技术。能够实时看到化学反应是化学、生物化学和生物学的重大挑战。它将改变我们的思维方式和我们所知道的东西。
英文摘要
We have set out to study an important new enzyme which makes a bond between two carbon atoms. The making of carbon carbon bonds is both the chemistry of life at its most basic and it is the central pillar of enzymatic chemistry. Being able to use an enzyme to make this bond, will make it possible to make new drugs. We have targeted so called C-nucleosides. These molecules trick bacteria and viruses into using them instead of the natural N-nucleosides. As a result of using these molecules, viruses and bacteria are killed. The carbon carbon bond is absolutely key to these molecules, it prevents the bacteria and virus from degrading the compound. These C-nucleosides are used by nature but they are hard to make, hence the need for new ways such as enzymes to make them. The system we are studying is also appealing because we can use it to study the grand challenge of watching chemistry in real time. Chemist occurs in around 1 billionth of second, far to fast for most techniques to see but the new X-ray free electron laser finishes experiments in around 1 trillionth of second, allowing us to see for the first time an enzyme catalysed chemical reaction. This ground breaking experiment will require a lot of preparation and new technologies which the grant will develop. Being able to see in real time a chemical reaction is a grand challenge of chemistry, biochemistry and biology. It will change how we think and what we know.
期刊论文(6)
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DOI:
10.1098/rsob.220287
发表时间:
2023-01
期刊:
Open biology
影响因子:
5.8
作者:
[]
通讯作者:
DOI:
10.1039/d0cc02834g
发表时间:
2020-07-14
期刊:
Chemical communications (Cambridge, England)
影响因子:
--
作者:
[Gao S, Radadiya A, Li W, Liu H, Zhu W, de Crécy-Lagard V, Richards NGJ, Naismith JH]
通讯作者:
Naismith JH
DOI:
10.1098/rsos.211016
发表时间:
2021-09
期刊:
Royal Society open science
影响因子:
3.5
作者:
[Girt GC, Lakshminarayanan A, Huo J, Dormon J, Norman C, Afrough B, Harding A, James W, Owens RJ, Naismith JH]
通讯作者:
Naismith JH
DOI:
10.1101/2020.03.26.009662
发表时间:
2020-03
期刊:
bioRxiv
影响因子:
--
作者:
[Sisi Gao;Ashish Radadiya;Wenbo Li;Huanting Liu;Wen Zhu;V. de Crécy-Lagard;N. Richards;J. Naismith]
通讯作者:
Sisi Gao;Ashish Radadiya;Wenbo Li;Huanting Liu;Wen Zhu;V. de Crécy-Lagard;N. Richards;J. Naismith
C-C Bond Formation (Li et al.) ESM from Experimental and computational snapshots of C-C bond formation in a C-nucleoside synthase
C-C 键形成(Li 等人)来自 C-核苷合酶中 C-C 键形成的实验和计算快照的 ESM
DOI:
10.6084/m9.figshare.21708000
发表时间:
2022
期刊:
影响因子:
--
作者:
[Li W]
通讯作者:
Li W
共 6 条
Rosalind Franklin Institute Core Capital Award
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RFI Phase 2
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Integrating confocal microscopy and cryo plasma FIB milling for tomography
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Design of a CMOS Sensor for Electron Microscopy
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Capital funding for NMR
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资助金额:$99.11万
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Capital funding for Helical Tomography
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批准号:EP/T012013/1
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Capital funding for Spotiton
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Recurrent funding for the RFI 2019 to 2021
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批准号:EP/T012021/1
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项目类别:Research Grant
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资助金额:$3777.05万
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The enzymatic methylation of the peptide bond
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Structural Biology in the RFI
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资助金额:$210.18万
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负责人:James Naismith
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Enhanced productivity and functionality of Modified Ribosomally Produced Peptides (M-RIPPs)
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批准号:BB/M028461/2
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资助金额:$18.28万
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负责人:James Naismith
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依托单位:
Enhanced productivity and functionality of Modified Ribosomally Produced Peptides (M-RIPPs)
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批准号:BB/M028461/1
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项目类别:Research Grant
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资助金额:$42.11万
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The human serine palmitoyltransferase (SPT) complex; specificity, structure, regulation and inhibition
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批准号:BB/M001679/1
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项目类别:Research Grant
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资助金额:$11.7万
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财政年份:2015
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负责人:James Naismith
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Exploring the mechanism and scope of the enzymatic formation of five membered ring
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批准号:BB/K015508/1
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资助金额:$63.81万
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财政年份:2013
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负责人:James Naismith
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依托单位:
13TSB_SynBio:Enhanced discovery and scalable synthesis of therapeutic cyclic peptides
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Elucidation of the bacterial sphingolipid biosynthetic pathway in Sphingomonas wittichii
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Conformational states of membrane proteins: Technology development for bioscience
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负责人:James Naismith
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CCP4: Low resolution complexes; handling difficult data; empowering structural biologists and supporting UK structural biology
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负责人:James Naismith
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CCP4 - Collaborative Computing Project in structural biology
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负责人:James Naismith
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Serine palmitoyltransferase / structure and function of the first enzyme in sphingolipid biosynthesis
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项目类别:Research Grant
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负责人:James Naismith
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国内基金
海外基金
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