Studies of the O-GlcNAc Modification

O-GlcNAc 修饰的研究

• 批准号: BB/F007124/1
• 负责人: Gideon Davies
• 金额: $ 64.92万
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF007124%2F1
• 关键词: Studies; GlcNAc; Modification

The sequencing of the human genome revealed a frightening observation. On the face of it, humans are not very complex at all: only 20-25,000 genes. Yet, as we all know, humans ARE complex organisms. This complexity is derived, in part, from chemical events that take place withing our cells which serves to expand the complexity of proteins - the products of these these 20,000 genes. One of the most important modifications that can take place withing cells is glycosylation of proteins with a sugar called N-acetylglucosamine. This is a dynamic modification: sugars can be put on and taken off in response to diverse stimuli including diet, hormones etc. These modifications are also very important in that it controls the function of the healthy cell. Furthermore, aberent states of modifications are linked to diseases such as cancer, and diabetes. The research proposed in this grant seeks to understand the chemistry and biochemistry of this N-acetylglucosamine modification. This will allow researchers to probe the biology of the healthy cell and also allow the design and exploitation of chemical molecules to inform our knowledge of disease processes.

人类基因组测序揭示了一个可怕的观察结果。从表面上看，人类一点也不复杂：只有20- 25，000个基因。众所周知，人类是复杂的生物。这种复杂性部分来自于我们细胞内发生的化学反应，这些化学反应扩大了蛋白质的复杂性，蛋白质是这2万个基因的产物。在细胞内发生的最重要的修饰之一是用一种叫做N-乙酰葡糖胺的糖对蛋白质进行糖基化。这是一个动态的修改：糖可以在响应不同的刺激，包括饮食，激素等，这些修改也是非常重要的，因为它控制健康细胞的功能。此外，异常的修饰状态与癌症和糖尿病等疾病有关。这项研究旨在了解这种N-乙酰葡糖胺修饰的化学和生物化学。这将使研究人员能够探测健康细胞的生物学，并允许设计和利用化学分子来告知我们对疾病过程的了解。

项目成果

Inhibition of O-GlcNAcase using a potent and cell-permeable inhibitor does not induce insulin resistance in 3T3-L1 adipocytes.

• DOI: 10.1016/j.chembiol.2010.07.006
• 发表时间: 2010-09-24
• 期刊: Chemistry & biology
• 作者: Macauley MS;He Y;Gloster TM;Stubbs KA;Davies GJ;Vocadlo DJ
• 通讯作者: Vocadlo DJ

Three-dimensional structure of a Streptomyces sviceus GNAT acetyltransferase with similarity to the C-terminal domain of the human GH84 O-GlcNAcase.

• DOI: 10.1107/s1399004713029155
• 发表时间: 2014-01
• 期刊: Acta crystallographica. Section D, Biological crystallography
• 作者: He Y;Roth C;Turkenburg JP;Davies GJ
• 通讯作者: Davies GJ