A disulfide redox switch mechanism regulates glycoside hydrolase function
Marcele Pandeló Martins1, Gustavo Henrique Martins1,2, Felipe Jun Fuzita1
1Brazilian Biorenewables National Laboratory (LNBR), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, São Paulo, Brazil.
Nature Communications
|January 6, 2026
Summary
Glycoside hydrolase activity is controlled by a reversible disulfide bond switch. This redox regulation mechanism impacts protein folding, stability, and function, with broad biotechnological implications.
Area of Science:
- Biochemistry
- Structural Biology
- Enzymology
Background:
- Disulfide bonds are crucial post-translational modifications regulating protein structure and function.
- Glycoside hydrolases (GHs) play key roles in carbohydrate metabolism.
Purpose of the Study:
- To investigate the redox regulation of a GH2 family glycoside hydrolase.
- To elucidate the structural basis for activity control via a disulfide bond.
Main Methods:
- X-ray crystallography
- Cryo-electron microscopy (cryo-EM)
- Biochemical assays
Main Results:
- The GH2 enzyme exhibits reversible redox regulation through an intramolecular disulfide bond.
- Oxidized state shows disordered active site loops and misaligned catalytic residues, leading to inactivity.
- Reduced state reveals an ordered active site, enabling substrate binding and catalysis via a Koshland retaining mechanism.
Conclusions:
- A disulfide bond acts as a redox switch, controlling glycoside hydrolase activity through an order-disorder mechanism.
- This regulation impacts carbohydrate metabolism, microbial adaptation, and offers biotechnological potential.
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