Bioinformatics-Facilitated Identification of Novel Bacterial Sulfoglycosidases That Hydrolyze 6-Sulfo-N-acetylglucosamine

Dong, Mochen, Chen, Zhuoyun, He, Yuan ORCID: https://orcid.org/0000-0002-1712-0776, Zallot, Rémi ORCID: https://orcid.org/0000-0002-7317-1578 and Jin, Yi ORCID: https://orcid.org/0000-0002-6927-4371 (2024) Bioinformatics-Facilitated Identification of Novel Bacterial Sulfoglycosidases That Hydrolyze 6-Sulfo-N-acetylglucosamine. ACS Bio & Med Chem Au, 4 (6). pp. 342-352. ISSN 2694-2437

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Abstract

Glycan sulfation is a widespread postglycosylation modification crucial for modulating biological functions including cellular adhesion, signaling, and bacterial colonization. 6-Sulfo-β-GlcNAcases are a class of enzyme that alters sulfation patterns. Such changes in sulfation patterns are linked to diseases such as bowel inflammation, colitis, and cancer. Despite their significance, 6-sulfo-β-GlcNAcases, which cleave β-linked 6-sulfo-N-acetylglucosamine (6S-GlcNAc), have been but rarely identified. This scarcity results mainly from the short, diverse, and distinctive sulfate-binding motifs required for recognition of the 6-sulfate group in 6S-GlcNAc in addition to the conserved GH20 family features. In this study, we discovered 6-sulfo-β-GlcNAcases and assigned two novel sulfate-binding motifs by the use of comparative genomics, structural predictions, and activity-based screening. Our findings expand the known microbiota capable of degrading sulfated glycans and add significant enzymes to the tool kit for analysis and synthesis of sulfated oligosaccharides.