Structure and function of bacterial glycosyltransferase enzymes

细菌糖基转移酶的结构和功能

• 批准号: 3074-2010
• 负责人: Whitfield, Christopher
• 金额: $ 6.99万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=520539
• 关键词: Structure; function; bacterial; glycosyltransferase; enzymes

Many different macromolecules containing complex carbohydrates (glycoconjugates) are found on the surfaces of living cells. These structures play crucial roles in the interactions between the cell and its environment, or in communications and interactions between one cell and another. Glycoconjugates on the surfaces of bacteria are important in survival against factors in the environment, or against the protective responses of mammalian or plant hosts. The function of a particular glycoconjugate is often dictated by its structure. The tremendous diversity of glycoconjugate structures results from the activity and specificity of enzymes involved in their formation; these enzymes are known as glycosyltransferases. Despite the importance of glycosyltransferases in biology, we have only a limited knowledge of their mechanisms of action and the structural features that dictate their specificity. We propose a detailed molecular analysis of several glycosyltransferases, to address different original questions about their action and specificity. We will focus on some novel bacterial systems where my laboratory has developed considerable expertise over the last 25 years. The information arising from these studies will be of fundamental importance and is predicted to have a broad impact on our understanding of the synthesis of glycoconjugates in bacteria and other biological systems. At a practical level, such information represents a significant step toward the ability to modulate glycosyltransferase activities to engineer tailor-made glycoconjugate structures with specific industrial or clinical applications.

活细胞表面存在许多不同的含有复杂碳水化合物的大分子。这些结构在细胞与其环境之间的相互作用中，或在一个细胞与另一个细胞之间的交流和相互作用中发挥着至关重要的作用。细菌表面的糖偶联物对于抵抗环境因素或哺乳动物或植物宿主的保护性反应具有重要意义。一种特定的糖偶联物的功能通常由其结构决定。糖共轭结构的巨大多样性源于参与其形成的酶的活性和特异性；这些酶被称为糖基转移酶。尽管糖基转移酶在生物学上很重要，但我们对其作用机制和决定其特异性的结构特征知之甚少。我们建议对几种糖基转移酶进行详细的分子分析，以解决关于它们的作用和特异性的不同原始问题。我们将把重点放在一些新的细菌系统上，在过去的25年里，我的实验室已经在这些系统上发展了相当多的专业知识。这些研究产生的信息将具有基本的重要性，预计将对我们理解细菌和其他生物系统中糖复合体的合成产生广泛的影响。在实践层面上，这些信息代表着朝着调节糖基转移酶活性的能力迈出了重要的一步，以设计具有特定工业或临床应用的定制糖共轭结构。