Fundamental biochemistry of N-glycosylationand the dolichol cycle

N-糖基化和多醇循环的基础生物化学

• 批准号: 2270056
• 金额: --
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2270056
• 关键词: Fundamental; biochemistry; glycosylationand; dolichol; cycle

The addition of sugars to proteins is an essential and highly regulated process in healthy humans. N-glycosylation describes the process in which sugar moieties are added to asparagine residues in a protein, and has important functions in protein stability, localisation, and function, with defects in many of the steps in N-glycosylation leading to congenital disorders of glycosylation. Sugar molecules destined to be used in N-glycosylation as well as in other cellular processes, are docked to the membrane of the endoplasmic reticulum inside human cells, on a lipid molecule called dolichol. Many of the enzymes involved in the early stages of N-glycosylation and in the synthesis and recycling of dolichol carrier remain uncharacterised in the literature, with most work focussing on yeast homologs. In many cases this is due to the difficulty of accessing either the enzyme or substrates. This project aims to address this by making substrate derivatives and using them for biochemical, biophysical and structural analysis of key enzymes. By looking at the mechanisms of each catalyst alone and also together in complexes, we will assess the dynamics between the enzymes and build a biochemical model of events in early N-glycosylation and the dolichol cycle.

向蛋白质中添加糖是健康人体中必不可少的高度调节过程。N-糖基化描述了糖部分被添加到蛋白质中的天冬酰胺残基的过程，并且在蛋白质稳定性、定位和功能方面具有重要功能，其中N-糖基化中的许多步骤中的缺陷导致先天性糖基化障碍。用于N-糖基化以及其他细胞过程的糖分子停靠在人类细胞内内质网的膜上，位于称为多萜醇的脂质分子上。许多参与N-糖基化的早期阶段以及多萜醇载体的合成和再循环的酶在文献中仍然未被表征，大多数工作集中在酵母同系物上。在许多情况下，这是由于难以获得酶或底物。该项目旨在通过制造底物衍生物并将其用于关键酶的生物化学，生物物理和结构分析来解决这一问题。通过单独观察每种催化剂的机制，以及在复合物中的机制，我们将评估酶之间的动力学，并建立早期N-糖基化和多萜醇循环中事件的生化模型。