Conformational gating mechanism for processive catalysis of β(1,3)-glucans

Processive catalysis is a fundamental molecular mechanism to build and dismantle complex biopolymers such as nucleic acids, proteins and carbohydrates, underpinning a myriad of biotechnological applications. Here, we uncover a processive mechanism for the breakdown of β(1,3)-glucans, a widespread carbohydrate class. This mechanism involves a dynamic active site, which adopts a tunnel-like conformation upon substrate binding. For product release, the disruption of a salt bridge triggers an open conformation that interacts with the remnant substrate, essential for subsequent catalytic cycles. Molecular simulations reveal that this processive cleavage involves a non-canonical sugar conformation, a characteristic hitherto limited to exo-acting enzymes. Together, these findings establish the mechanistic basis for β(1,3)-glucan processive catalysis, from substrate recognition to tunnel formation, nucleophilic attack, intermediate state stabilization, product release and translocation. Ultimately, this work broadens the knowledge of β(1,3)-glucan breakdown, demonstrating that enzymatic processive catalysis is a conserved evolutionary strategy across all major classes of β-glucans.