8ai5

Crystal structure of radical SAM epimerase EpeE C223A mutant from Bacillus subtilis with [4Fe-4S] clusters, S-adenosyl-L-homocysteine and RiPP peptide 6 bound

spinqualitylabelsall models 8ai5, resolution 2.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8ai5 is a 4 chain structure with sequence from Bacillus subtilis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.15Å Ligands: EDO, PEG, SAH Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function YYDG_BACSU Required for production of the modified peptide YydF (Probable). May activate a metalloenzyme (Potential). Publication Abstract from PubMed 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. Structural and mechanistic basis for RiPP epimerization by a radical SAM enzyme.,Kubiak X, Polsinelli I, Chavas LMG, Fyfe CD, Guillot A, Fradale L, Brewee C, Grimaldi S, Gerbaud G, Thureau A, Legrand P, Berteau O, Benjdia A Nat Chem Biol. 2024 Mar;20(3):382-391. doi: 10.1038/s41589-023-01493-1. Epub 2023 , Dec 29. PMID:38158457 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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