Structural analysis of the sulfatase AmAS from Akkermansia muciniphila

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 rat...

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Published in:Acta crystallographica. Section D, Biological crystallography. Biological crystallography., 2021-12, Vol.77 (12), p.1614-1623
Main 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
Format: Article
Language:English
Subjects:
Acetylglucosamine - metabolism
Akkermansia - enzymology
Akkermansia muciniphila
Bacteria
Binding
Biodegradation
Catalysis
Crystal structure
Crystallography, X-Ray
Digestive system
Digestive tract
human gut
Humans
Immune response
Molecular Docking Simulation
Mucin
mucins
Mucosa
Nucleotide sequence
Nutrients
Polysaccharides
Protein Conformation
protein structure
Sequence Alignment
Structural analysis
Substrate Specificity
Substrates
sulfatases
Sulfatases - chemistry
Sulfatases - isolation & purification
Sulfatases - metabolism
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Summary: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. 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.
ISSN:2059-7983
0907-4449
2059-7983
1399-0047
DOI:10.1107/S2059798321010317