Abstract：
Sialic acids play crucial roles in cell surface glycans of both eukaryotic and prokaryotic organisms, mediating various biological processes, including cell-cell interactions, development, immune response, oncogenesis and host-pathogen interactions. This review focuses on the β-anomeric form of N-acetylneuraminic acid (Neu5Ac), particularly its binding affinity towards various proteins, as elucidated by solved protein structures. Specifically, we delve into the binding mechanisms of Neu5Ac to proteins involved in sequestering and transporting Neu5Ac in Gram-negative bacteria, with implications for drug design targeting these proteins as antimicrobial agents. Unlike the initial assumptions, structural analyses revealed significant variability in the Neu5Ac binding pockets among proteins, indicating diverse evolutionary origins and binding modes. By comparing these findings with existing structures from other systems, we can effectively highlight the intricate relationship between protein structure and Neu5Ac recognition, emphasizing the need for tailored drug design strategies to inhibit Neu5Ac-binding proteins across bacterial species.
摘要：
唾液酸在真核生物和原核生物的细胞表面聚糖中起着至关重要的作用，介导各种生物过程，包括细胞间的相互作用，发展,免疫反应，肿瘤发生和宿主-病原体相互作用。这篇综述的重点是N-乙酰神经氨酸（Neu5Ac）的β-异头形式，特别是它对各种蛋白质的结合亲和力，如解决的蛋白质结构所阐明的。具体来说,我们深入研究了Neu5Ac与革兰氏阴性细菌中隔离和转运Neu5Ac的蛋白质的结合机制，对靶向这些蛋白质作为抗菌剂的药物设计有影响。与最初的假设不同，结构分析揭示了蛋白质之间Neu5Ac结合口袋的显着变异性，表明不同的进化起源和结合模式。通过将这些发现与其他系统的现有结构进行比较，我们可以有效地突出蛋白质结构和Neu5Ac识别之间的复杂关系，强调需要定制的药物设计策略来抑制跨细菌物种的Neu5Ac结合蛋白。
