Mechanistic Investigations of Anaerobic Sulfatase-Maturating Enzyme: Direct C β H-Atom Abstraction Catalyzed by a Radical AdoMet Enzyme

Alhosna Benjdia (1) , Corine C. Sandstrom (2) , Hubert Vaudry (3) , Olivier Berteau (1) , Jérôme Leprince (3, 4, 5) , Corine Sandström

1 MICALIS - MICrobiologie de l'ALImentation au Service de la Santé
2 Dept Chem
3 Neuroendocrinologie cellulaire et moléculaire
4 DC2N - Différenciation et communication neuronale et neuroendocrine
5 DC2N - Différenciation et communication neuronale et neuroendocrine

Sulfatases are unique in requiring an essential post-translational modification of a critical active-site cysteinyl or seryl residue to 3-oxoalanine usually called C alpha-formylglycine (FGly). This post-translational modification is catalyzed anaerobically by anaerobic Sulfatase Maturating Enzyme (anSME), a member of the radical AdoMet superfamily. Using a new labeled substrate, we demonstrate that anSME uses a 5'-deoxyadenosyl radical to catalyze direct H-atom abstraction from the substrate. We thus established that anSMEs are the first radical AdoMet enzymes catalyzing a post-translational modification involving C(beta) H-atom abstraction from an active site cysteinyl or seryl residue. This mechanistic study allowed us to decipher the first steps of the mechanism of this new radical AdoMet enzyme family.

Domains: Chemical Sciences; Medicinal Chemistry; Life Sciences [q-bio]; Cellular Biology; Cell Behavior [q-bio.CB]; Life Sciences [q-bio]; Neurons and Cognition [q-bio.NC]; Neurobiology; Life Sciences [q-bio]; Pharmaceutical sciences; Pharmacology

Alhosna Benjdia, Corine C. Sandstrom, Hubert Vaudry, Olivier Berteau, Jérôme Leprince, et al.. Mechanistic Investigations of Anaerobic Sulfatase-Maturating Enzyme: Direct C β H-Atom Abstraction Catalyzed by a Radical AdoMet Enzyme. Journal of the American Chemical Society, 2009, 131 (24), pp.8348-8349. ⟨10.1021/ja901571p⟩. ⟨hal-01960686⟩