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Structural and mechanistic basis for RiPP epimerization by a radical SAM enzyme.
Kubiak, Xavier; Polsinelli, Ivan; Chavas, Leonard M G; Fyfe, Cameron D; Guillot, Alain; Fradale, Laura; Brewee, Clémence; Grimaldi, Stéphane; Gerbaud, Guillaume; Thureau, Aurélien; Legrand, Pierre; Berteau, Olivier; Benjdia, Alhosna.
Afiliación
  • Kubiak X; Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, ChemSyBio, Jouy-en-Josas, France.
  • Polsinelli I; Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, ChemSyBio, Jouy-en-Josas, France.
  • Chavas LMG; Nagoya University, Nagoya, Japan.
  • Fyfe CD; Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, ChemSyBio, Jouy-en-Josas, France.
  • Guillot A; Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, ChemSyBio, Jouy-en-Josas, France.
  • Fradale L; Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, ChemSyBio, Jouy-en-Josas, France.
  • Brewee C; Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, ChemSyBio, Jouy-en-Josas, France.
  • Grimaldi S; Aix-Marseille Université, CNRS, BIP, IMM, IM2B, Marseille, France.
  • Gerbaud G; Aix-Marseille Université, CNRS, BIP, IMM, IM2B, Marseille, France.
  • Thureau A; Synchrotron SOLEIL, HelioBio Group, L'Orme des Merisiers, Saint-Aubin, France.
  • Legrand P; Synchrotron SOLEIL, HelioBio Group, L'Orme des Merisiers, Saint-Aubin, France.
  • Berteau O; Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, ChemSyBio, Jouy-en-Josas, France. olivier.berteau@inrae.fr.
  • Benjdia A; Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, ChemSyBio, Jouy-en-Josas, France. alhosna.benjdia@inrae.fr.
Nat Chem Biol ; 20(3): 382-391, 2024 Mar.
Article en En | MEDLINE | ID: mdl-38158457
ABSTRACT
D-Amino acid residues, found in countless peptides and natural products including ribosomally synthesized and post-translationally modified peptides (RiPPs), are critical for the bioactivity of several antibiotics and toxins. Recently, radical S-adenosyl-L-methionine (SAM) enzymes have emerged as the only biocatalysts capable of installing direct and irreversible epimerization in RiPPs. However, the mechanism underpinning this biochemical process is ill-understood and the structural basis for this post-translational modification remains unknown. Here we report an atomic-resolution crystal structure of a RiPP-modifying radical SAM enzyme in complex with its substrate properly positioned in the active site. Crystallographic snapshots, size-exclusion chromatography-small-angle x-ray scattering, electron paramagnetic resonance spectroscopy and biochemical analyses reveal how epimerizations are installed in RiPPs and support an unprecedented enzyme mechanism for peptide epimerization. Collectively, our study brings unique perspectives on how radical SAM enzymes interact with RiPPs and catalyze post-translational modifications in natural products.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: S-Adenosilmetionina / Productos Biológicos Idioma: En Revista: Nat Chem Biol Asunto de la revista: BIOLOGIA / QUIMICA Año: 2024 Tipo del documento: Article País de afiliación: Francia

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: S-Adenosilmetionina / Productos Biológicos Idioma: En Revista: Nat Chem Biol Asunto de la revista: BIOLOGIA / QUIMICA Año: 2024 Tipo del documento: Article País de afiliación: Francia