Structural analysis of the sulfatase AmAS from Akkermansia muciniphila. Issue 12 (30th November 2021)

• Record Type: Journal Article
• Authors: Li, Chang-Cheng; Tang, Xin-Yue; Zhu, Yi-Bo; Song, Ying-Jie; Zhao, Ning-Lin; Huang, Qin; Mou, Xing-Yu; Luo, Gui-Hua; Liu, Tong-Gen; Tong, Ai-Ping; Tang, Hong; Bao, Rui
• Is Part Of: Acta crystallographica. Volume 77:Issue 12(2021)
• Page Start: 1614
• Page End: 1623
• Publication Date: 2021-11-30
• Subjects: Akkermansia muciniphila -- sulfatases -- mucins -- protein structure -- human gut; X-ray crystallography -- Periodicals; Crystallography -- Periodicals; Molecular biology -- Periodicals; Molecular structure -- Periodicals; Biomolecules -- Structure -- Periodicals; Cytology -- Periodicals; Biomolecules -- Structure; Crystallography; Cytology; Molecular biology; Molecular structure; X-ray crystallography; Periodicals; 548
• DOI: 10.1107/S2059798321010317
• Languages: English
• ISSNs: 2059-7983

Abstract

Abstract : The crystal structure of the A. muciniphila arylsulfatase AmAS is reported and some structural regularity of substrate binding and specificity was noted. Insights into the catalytic mechanism of mucin‐desulfating sulfatases in A. muciniphila are also provided based on this regularity. Abstract : 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.