Conformational changes in formylglycine-generating enzyme during the catalytic cycle: Role of reducing agent and calcium

Beschreibung

Formylglycine generation, a unique process necessary for the activation of sulfatases, is a cotranslational event conserved from pro- to eukaryotes and is defined by the modification of the cysteine residue in the CxPxR motif of largely unfolded sulfatase polypeptides to C-formylglycine (FGly). This process is confined to the endoplasmic reticulum (ER) in eukaryotes and catalyzed by the formylglycine-generating enzyme (FGE), a resident protein of the ER. Mutations in FGE, that impair FGly generation, lead to production of inactive sulfatases that manifests into an inherited metabolic disorder termed multiple sulfatase deficiency (MSD) in humans. Although FGE has been proposed to function as a DTT and calcium dependent monooxygenase, the precise mechanism has remained enigmatic.

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Sarfaraz Alam

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Formylglycine generation enzyme Multiple sulfatase deficiency in vitro activity

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