Structure and function of bacterial glycosyltransferase enzymes

在活细胞的表面发现了许多含有复杂碳水化合物（糖缀合物）的不同大分子。这些结构在细胞和环境之间的相互作用，或者在细胞和另一个细胞之间的通信和相互作用中起着至关重要的作用。细菌表面的糖缀合物对于抵抗环境因素或抵抗哺乳动物或植物宿主的保护反应的生存是重要的。特定糖缀合物的功能通常由其结构决定。糖缀合物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中的重要性，但我们对其作用机制和决定其特异性的结构特征的了解有限。我们提出了一个详细的分子分析几种糖基转移酶，以解决不同的原始问题，关于它们的作用和特异性。我们将专注于一些新的细菌系统，我的实验室在过去的25年里已经发展了相当多的专业知识。从这些研究中获得的信息将具有根本性的重要性，预计将对我们对细菌和其他生物系统中糖缀合物合成的理解产生广泛的影响。在实践层面上，这些信息代表着向调节糖基转移酶活性的能力迈出了重要的一步，从而设计出具有特定工业或临床应用的定制糖缀合物结构。

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.