Structural and cellular studies on O-GlcNAc and related glycosylations

O-GlcNAc 及相关糖基化的结构和细胞研究

• 批准号: 1644614
• 金额: --
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1644614
• 关键词: Structural; cellular; studies; GlcNAc; related

The control of cellular function through the co- and post-translational O-GlcNAc modification is one of the emerging themes of modern cell biology. Of particular note is the link to neurodegenerative diseases, notably the tauopathies, where the modification stabilizes tau and reduced toxic aggregation and Parkinson's disease. The PhD will study the molecular basis of the O-GlcNAc, and related, glycosylations through a combination of X-ray crystallography, inhibitor design and analysis, rational protein engineering and chemical biology. The ultimate goal is to provide a structural and mechanistic description of the human enzyme system and to use this to inform cellular studies probing enzyme inhibition in a therapeutic context.

通过共翻译和翻译后的O-GlcNAc修饰来控制细胞功能是现代细胞生物学的新兴主题之一。特别值得注意的是与神经退行性疾病的联系，特别是tauopathy，其中修饰稳定tau并减少毒性聚集和帕金森病。博士将通过结合X射线结晶学、抑制剂设计和分析、合理蛋白质工程和化学生物学来研究O-GlcNAc和相关糖基化的分子基础。最终目标是提供对人类酶系统的结构和机制的描述，并利用这一描述为细胞研究提供信息，探索治疗背景下的酶抑制。

项目成果

A Family of Dual-Activity Glycosyltransferase-Phosphorylases Mediates Mannogen Turnover and Virulence in Leishmania Parasites.

• DOI: 10.1016/j.chom.2019.08.009
• 发表时间: 2019-09
• 期刊: Cell host & microbe
• 影响因子: 30.3
• 作者: M. F. Sernee;J. Ralton;T. Nero;Lukasz F Sobala;Joachim Kloehn;Marcel A. Vieira-Lara;Simon A. Cobbold;L. Stanton;D. Pires;E. Hanssen;A. Males;T. Ward;L. M. Bastidas;Phillip L van der Peet;M. Parker;D. Ascher;Spencer J. Williams;G. Davies;M. McConville

Conformational Analysis of the Mannosidase Inhibitor Kifunensine: A Quantum Mechanical and Structural Approach

• DOI: 10.1002/cbic.201700166
• 发表时间: 2017-08-04
• 期刊: CHEMBIOCHEM
• 影响因子: 3.2
• 作者: Males, Alexandra;Raich, Lluis;Davies, Gideon J.
• 通讯作者: Davies, Gideon J.

Structural studies of a surface-entropy reduction mutant of O-GlcNAcase

O-GlcNAcase 表面熵减少突变体的结构研究

• DOI: 10.1107/s2059798318016595
• 发表时间: 2019
• 期刊: Acta Crystallographica Section D Structural Biology
• 作者: Males A

Conformational Behaviour of Azasugars Based on Mannuronic Acid.

基于甘露糖醛酸的 Azasugar 的构象行为。

• DOI: 10.1002/cbic.201700080
• 发表时间: 2017
• 期刊: a European journal of chemical biology
• 作者: Van Rijssel ER