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cc-by (c) Sagiroglugil, Mert et al., 2024
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/222480

An Unusual His/Asp Dyad Operates Catalysis in Agar-Degrading Glycosidases

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Agarose motifs, found in agars present in the cell walls of red algae, consist of alternating units of d-galactose (G) and α-3,6-anhydro-l-galactose (LA). Glycoside hydrolases from family 117 (GH117) cleave the terminal α-1,3-glycosidic bonds, releasing LA units. Structural studies have suggested that these enzymes use unconventional catalytic machinery, involving a histidine (His302) as a general acid rather than a carboxylic residue as in most glycosidases. By means of quantum mechanics/molecular mechanics metadynamics, we investigated the reaction mechanism of Phocaeicola plebeius GH117, confirming the catalytic role of His302. This residue shares a proton with a neighbor aspartate residue (Asp320), forming a His/Asp dyad. Our study also reveals that, even though the sugar unit at the –1 subsite (LA) can adopt two conformations, 4C1 and 1,4B, only the latter is catalytically competent, defining a 1,4B → [4E]‡ → 1,4B (→ 4C1) conformational itinerary. This mechanism may be applicable to similar enzymes with a His/Asp dyad in their active sites, such as GH3 β-N-acetylglucosaminidase and GH156 sialidase. These insights enhance our understanding of glycosidase catalytic strategies and could inform the engineering of enzymes for the more efficient processing of seaweed.

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SAGIROGLUGIL, Mert, NIN HILL, Alba, FICKO-BLEAN, Elizabeth, ROVIRA I VIRGILI, Carme. An Unusual His/Asp Dyad Operates Catalysis in Agar-Degrading Glycosidases. _ACS Catalysis_. 2024. Vol. 14, núm. 22, pàgs. 16897-16904. [consulta: 8 de gener de 2026]. ISSN: 2155-5435. [Disponible a: https://hdl.handle.net/2445/222480]

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