9PM4

The structure of O-glycopeptidase BcM60C from Bacteroides caccae in complex with a 6-sialo core 1 glycan

Summary for 9PM4

• Entry DOI: 10.2210/pdb9pm4/pdb
• Descriptor: O-glycopeptidase BcM60C, beta-D-galactopyranose-(1-3)-[N-acetyl-alpha-neuraminic acid-(2-6)]2-acetamido-2-deoxy-alpha-D-galactopyranose, SERINE, ... (7 entities in total)
• Functional Keywords: glycoprotease, o-glycopeptidase, bacteroides caccae, peptidase, glycan, mucin, hydrolase
• Biological source: Bacteroides caccae ATCC 43185
• Total number of polymer chains: 1
• Total formula weight: 61272.90

Authors

Boraston, A.B.,Pluvinage, B. (deposition date: 2025-07-16, release date: 2026-06-17, Last modification date: 2026-07-15)

Primary citation

Pluvinage, B.,Bourdon, K.,Canil, O.,Deventer, A.,Alvarez, B.,Mihalynuk, L.,Thompson, N.,Wakarchuk, W.,Boraston, A.B.
Substrate recognition and cleavage by mucin degrading O-glycopeptidases from the gut microbe Bacteroides caccae.
J.Biol.Chem., 302:113222-113222, 2026

PubMed Abstract: O-glycopeptidases are enzymes that hydrolyze the peptide bonds in glycoproteins by a mechanism that involves specific recognition of O-linked glycans on the substrate. Bacteroides caccae, an accomplished mucin degrader, is a member of the human gut microbiota with sixteen genes encoding putative O-glycopeptidases in the peptidase_M60 family. At present, the diversity of substrate selectivity in O-glycopeptidases is not well-understood nor is the rationale behind their expansion in bacteria such as B. caccae. Here we reveal the activity and diversity of the peptidase_M60 O-glycopeptidases encoded in the B. caccae genome. At least thirteen of the sixteen peptidase_M60 genes encode active mucinolytic enzymes. Targeted functional studies by a high-throughput FRET screen combined with detailed kinetic analyses reveal that five examples in an uncharacterized clade of peptidase_M60 proteins are specifically O-glycopeptidases with different substrate selectivities despite their relatively high degree of relatedness. Structural analyses of these enzymes, including bound complexes, reveal new insight into the molecular underpinnings of O-glycopeptidase diversity. This highlights the larger context of how varied the selectivity of peptidase_M60 O-glycopeptidases can be for the glycan moiety and/or the peptide portion of the substrates, and why mucin degraders like B. caccae diversify O-glycopeptidase substrate repertoires to potentially maximize breakdown of this extraordinarily complex polymer.

PubMed: 42248462
DOI: 10.1016/j.jbc.2026.113222

Experimental method

X-RAY DIFFRACTION (1.55 Å)