Akkermansia muciniphila, an anaerobic Gram-negative bacterium, is a major intestinal commensal bacterium that can modulate the host immune response. It colonizes the mucosal layer and produces nutrients for the gut mucosa and other commensal bacteria. It is believed that mucin desulfation is the rate-limiting step in the mucin-degradation process, and bacterial sulfatases that carry out mucin desulfation have been well studied. However, little is known about the structural characteristics of A. muciniphila sulfatases. Here, the crystal structure of the premature form of the A. muciniphila sulfatase AmAS was determined. Structural analysis combined with docking experiments defined the critical active-site residues that are responsible for catalysis. The loop regions I–V were proposed to be essential for substrate binding. Structure-based sequence alignment and structural superposition allow further elucidation of how different subclasses of formylglycine-dependent sulfatases (FGly sulfatases) adopt the same catalytic mechanism but exhibit diverse substrate specificities. These results advance the understanding of the substrate-recognition mechanisms of A. muciniphila FGly-type sulfatases. Structural variations around the active sites account for the different substrate-binding properties. These results will enhance the understanding of the roles of bacterial sulfatases in the metabolism of glycans and host–microbe interactions in the human gut environment.

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Akkermansia muciniphila 硫酸酯酶 AmAS 的结构分析

Akkermansia muciniphila是一种厌氧革兰氏阴性菌，是一种主要的肠道共生菌，可以调节宿主的免疫反应。它定植于粘膜层并为肠道粘膜和其他共生细菌产生营养。人们认为粘蛋白脱硫是粘蛋白降解过程中的限速步骤，并且已经对进行粘蛋白脱硫的细菌硫酸酯酶进行了很好的研究。然而，关于A. muciniphila硫酸酯酶的结构特征知之甚少。在这里， A. muciniphila的过早形式的晶体结构测定硫酸酯酶 AmAS。结合对接实验的结构分析确定了负责催化的关键活性位点残基。环区 I-V 被认为是底物结合所必需的。基于结构的序列比对和结构叠加允许进一步阐明甲酰甘氨酸依赖性硫酸酯酶（FGly 硫酸酯酶）的不同亚类如何采用相同的催化机制但表现出不同的底物特异性。这些结果促进了对A. muciniphila底物识别机制的理解FGly 型硫酸酯酶。活性位点周围的结构变化解释了不同的底物结合特性。这些结果将增强对细菌硫酸酯酶在聚糖代谢和人类肠道环境中宿主-微生物相互作用中的作用的理解。