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Tripping the light fantastic: elucidating global protein structural change correlated with chemical change across the femtosecond to second timescale

奇妙的奇妙之旅：阐明飞秒到秒时间尺度内与化学变化相关的整体蛋白质结构变化

基本信息

批准号：
EP/S030336/1
负责人：
Nigel Scrutton
金额：
$ 180.93万
依托单位：
University of Manchester
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2019
资助国家：
英国
起止时间：
2019 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FS030336%2F1
关键词：
Tripping light fantastic elucidating global

项目摘要

At the heart of chemistry lies the process of atomic bond formation and breakage, an event that is very difficult to directly observe due to the extremely fast timescale and the very small nature of the atomic bond. In other words, the construction of a 'molecular camera' that might allow the recording of these fast and tiny events only recently become a reality. The advent of X-FEL (X-ray Free Electron Laser) systems has made the recording of such molecular movies a reality, although this remains an extremely technically challenging feat to achieve. Systems where atomic bond reorganisation is trigger by light are ideally suited as initial subjects for these cutting-edge studies as the researcher (ie the camera man) can control the event through (laser) illumination. We seek to determine how two distinct type of biological photoreceptors respond to light, coupling the initial atomic bond reorganisation to the transient change in protein structure that ulimately leads to a light-driven response by the organism. This will allow us to formulate new models for general protein dynamic behaviour, which will impact the areas of biocatalysis, biomaterials, therapeutic antibodies/protein production and the study of protein dynamic behaviour/misfolding in health and disease. Ultimately, the full characterisation of these photoreceptors will be combined with the rational engineering of these systems to produce a range of variants in terms of their response to light of various wavelenghts/colour. This will produce well-characterised light-responsive parts for control of bio-based production of high-value chemicals. The most desirable way to assert this control is through optogenetics: by using light as a non-invasive and non-toxic switch to modulate gene expression during continuous microbial fermentation, simple control of engineered biosynthetic pathways can be achieved.

化学的核心在于原子键形成和断裂的过程，由于极快的时间尺度和原子键非常小的性质，这一事件很难直接观察。换句话说，建造可以记录这些快速而微小的事件的“分子相机”直到最近才成为现实。 X-FEL（X 射线自由电子激光）系统的出现使记录此类分子电影成为现实，尽管这在技术上仍然是一项极具挑战性的壮举。由光触发原子键重组的系统非常适合作为这些前沿研究的初始主题，因为研究人员（即摄影师）可以通过（激光）照明来控制事件。我们试图确定两种不同类型的生物光感受器如何响应光，将最初的原子键重组与蛋白质结构的瞬时变化耦合起来，最终导致生物体产生光驱动的响应。这将使我们能够为一般蛋白质动态行为制定新模型，这将影响生物催化、生物材料、治疗性抗体/蛋白质生产以及健康和疾病中蛋白质动态行为/错误折叠的研究领域。最终，这些光感受器的全面表征将与这些系统的合理工程相结合，以产生一系列对不同波长/颜色的光响应的变体。这将生产出特性良好的光响应部件，用于控制高价值化学品的生物基生产。实现这种控制的最理想的方法是通过光遗传学：通过使用光作为非侵入性和无毒的开关来调节连续微生物发酵过程中的基因表达，可以实现对工程生物合成途径的简单控制。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

An unusual light-sensing function for coenzyme B12 in bacterial transcription regulator CarH.

DOI：
10.1016/bs.mie.2021.12.010
发表时间：
2022
期刊：
Methods in enzymology
影响因子：
0
作者：
H. Poddar;D. Heyes;Shaowei Zhang;S. Hardman;M. Sakuma;N. Scrutton
通讯作者：
H. Poddar;D. Heyes;Shaowei Zhang;S. Hardman;M. Sakuma;N. Scrutton

Photoinduced Electron Transfer from a 1,4,5,6-Tetrahydro Nicotinamide Adenine Dinucleotide (Phosphate) Analogue to Oxidized Flavin in an Ene-Reductase Flavoenzyme.

DOI：
10.1021/acs.jpclett.3c00176
发表时间：
2023-04-06
期刊：
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
影响因子：
5.7
作者：
Speirs, Magnus;Hardman, Samantha J. O.;Iorgu, Andreea I.;Johannissen, Linus O.;Heyes, Derren J.;Scrutton, Nigel S.;Sazanovich, Igor, V;Hay, Sam
通讯作者：
Hay, Sam

A guide to time-resolved structural analysis of light-activated proteins.

光激活蛋白质的时间分辨结构分析指南。