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Characterization of an α-glucan-binding module from Flavobacterium johnsoniae as a founding member of carbohydrate-binding module family XXX

Widen, T.; McKee, L. S.; Koropatkin, N.; Larsbrink, J.

2026-01-31 biochemistry
10.64898/2026.01.30.702845 bioRxiv
Show abstract

Carbohydrate-binding modules (CBMs) play crucial roles in carbohydrate-active enzymes by promoting substrate recognition and proximity, particularly for insoluble polysaccharides. Here, we report the discovery and characterization of a novel {beta}-trefoil structured CBM associated with a GH87 -1,3-glucanase from Flavobacterium johnsoniae, which accordingly was designated FjCBMXXXGH87. The full-length enzyme efficiently hydrolyzed -1,3-glucan (mutan) and -1,3/-1,6-glucan (alternan), whereas the catalytic domain alone displayed reduced activity, indicating that FjCBMXXXGH87 enhances substrate interaction. Pull-down assays confirmed that FjCBMXXXGH87 binds -1,3-linked glucans, and structural investigation together with site-directed mutagenesis identified two distinct binding sites essential for protein-ligand interactions. Phylogenetic analysis showed that CBMXXX homologs are present together with enzymes from families GH87, GH13, GH16, and GH99, and potentially may comprise up to three binding sites. Together, these findings establish FjCBMXXXGH87 as the founding member of a new CBM family, which may have broad functional versatility in polysaccharide recognition. This discovery expands the repertoire of {beta}-trefoil CBMs and provides new insights into carbohydrate recognition strategies relevant to -glucan degradation.

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