PXD070002-1

PXD070002 is an original dataset announced via ProteomeXchange.

Title	A disulfide redox switch mechanism regulates glycoside hydrolase function
Description	Disulfide bond is a key post-translational modification involved in protein folding, stability, and functional regulation. While the structural role of disulfide bonds has been extensively studied in protein chemistry, their potential involvement in regulating catalytic activity of carbohydrate-active enzymes through redox switch mechanisms remains an untapped realm. In this work, we demonstrate that a glycoside hydrolase from the large family GH2 has its catalytic activity regulated via an intramolecular disulfide bond, adapting dynamically to redox fluctuations in its environment. The enzyme is inactive in its oxidized state, becoming active when reduced through a fully reversible process. Under oxidative conditions, multiple crystallographic structures showed that the disulfide bond formation induces a massive structural disorder in the active site, disrupting the substrate binding site and remarkably the acidic catalytic residues configuration. Conversely, high-resolution cryo-EM structure of the active (reduced) state revealed a notable well-structured active site with catalytic residues properly positioned for a classical Koshland retaining mechanism. This reversible order-disorder mechanism based on disulfide switch to regulate catalytic activity broadens our understanding regarding redox systems involved in carbohydrate breakdown and metabolism, which have implications for biotechnology and microbial biology.
HostingRepository	PRIDE
AnnounceDate	2025-10-30
AnnouncementXML	Submission_2025-10-30_14:42:09.760.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Felipe Fuzita
SpeciesList	scientific name: unclassified Eubacteriaceae; NCBI TaxID: NEWT:207769;
ModificationList	N-ethylmaleimide derivatized cysteine; biotinylated residue; L-cysteine sulfinic acid; monohydroxylated residue; L-cysteic acid (L-cysteine sulfonic acid); iodoacetamide derivatized residue
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-28 21:02:24	ID requested
⏵ 1	2025-10-30 14:42:10	announced

Dataset with its publication pending

submitter keyword: disulfide bond, protein dynamics, order-disorder mechanism, redox regulation, carbohydrate enzymology

Felipe Jun Fuzita
contact affiliation	National Laboratory of Biorenewables (LNBR), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, São Paulo, Brazil
contact email	felipe.fuzita@lnbr.cnpem.br
lab head
Felipe Fuzita
contact affiliation	CNPEM
contact email	felipe.fuzita@lnbr.cnpem.br
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD070002
     1. Label: PRIDE project
     2. Name: A disulfide redox switch mechanism regulates glycoside hydrolase function