Dataset Information

A previously uncharacterized O-glycopeptidase from Akkermansia muciniphila requires the Tn-antigen for cleavage of the peptide bond.

ABSTRACT: Akkermansia muciniphila is key member of the human gut microbiota that impacts many features of host health. A major characteristic of this bacterium is its interaction with host mucin, which is abundant in the gut environment, and its ability to metabolize mucin as a nutrient source. The machinery deployed by A. muciniphila to enable this interaction appears to be extensive and sophisticated, yet it is incompletely defined. The uncharacterized protein AMUC_1438 is encoded by a gene that was previously shown to be upregulated when the bacterium is grown on mucin. This uncharacterized protein has features suggestive of carbohydrate-recognition and peptidase activity, which led us to hypothesize that it has a role in mucin depolymerization. Here, we provide structural and functional support for the assignment of AMUC_1438 as a unique O-glycopeptidase with mucin-degrading capacity. O-glycopeptidase enzymes recognize glycans but hydrolyze the peptide backbone and are common in host-adapted microbes that colonize or invade mucus layers. Structural, kinetic, and mutagenic analyses point to a metzincin metalloprotease catalytic motif but with an active site that specifically recognizes a GalNAc residue α-linked to serine or threonine (i.e., the Tn-antigen). The enzyme catalyzes hydrolysis of the bond immediately N-terminal to the glycosylated residue. Additional modeling analyses suggest the presence of a carbohydrate-binding module that may assist in substrate recognition. We anticipate that these results will be fundamental to a wider understanding of the O-glycopeptidase class of enzymes and how they may contribute to host adaptation.

SUBMITTER: Medley BJ

PROVIDER: S-EPMC9513282 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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A previously uncharacterized O-glycopeptidase from Akkermansia muciniphila requires the Tn-antigen for cleavage of the peptide bond.

Medley Brendon J BJ Leclaire Leif L Thompson Nicole N Mahoney Keira E KE Pluvinage Benjamin B Parson Matthew A H MAH Burke John E JE Malaker Stacy S Wakarchuk Warren W Boraston Alisdair B AB

The Journal of biological chemistry 20220830 10

Akkermansia muciniphila is key member of the human gut microbiota that impacts many features of host health. A major characteristic of this bacterium is its interaction with host mucin, which is abundant in the gut environment, and its ability to metabolize mucin as a nutrient source. The machinery deployed by A. muciniphila to enable this interaction appears to be extensive and sophisticated, yet it is incompletely defined. The uncharacterized protein AMUC_1438 is encoded by a gene that was pre ...[more]

PMID: 36049519

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Dataset Information

A previously uncharacterized O-glycopeptidase from Akkermansia muciniphila requires the Tn-antigen for cleavage of the peptide bond.

Publications

A previously uncharacterized O-glycopeptidase from Akkermansia muciniphila requires the Tn-antigen for cleavage of the peptide bond.

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