A disulfide redox switch mechanism regulates glycoside hydrolase function.

ABSTRACT: Disulfide bonds are a key post-translational modification involved in protein folding, structural stability, and functional regulation. Here, we demonstrate that a glycoside hydrolase from the GH2 family undergoes reversible redox regulation through an intramolecular disulfide bond. The enzyme is inactive in its oxidized state and becomes active when reduced through a fully reversible process. Under oxidative conditions, multiple crystallographic and cryo-EM structures revealed a pronounced structural disorder in the active site, most prominent in the regulatory and catalytic loops, which disrupts the substrate binding site and, remarkably, the configuration of the acidic catalytic residues. Conversely, a high-resolution cryo-EM structure of the active (reduced) state unveiled a well-order

SUBMITTER: Martins MP 

PROVIDER: S-EPMC12770490 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature