8AI1
Crystal structure of radical SAM epimerase EpeE from Bacillus subtilis with [4Fe-4S] clusters and S-adenosyl-L-homocysteine bound.
Summary for 8AI1
| Entry DOI | 10.2210/pdb8ai1/pdb |
| Descriptor | Putative peptide biosynthesis protein YydG, IRON/SULFUR CLUSTER, S-ADENOSYL-L-HOMOCYSTEINE, ... (6 entities in total) |
| Functional Keywords | radical sam, metalloenzyme, iron-sulfur, ripp, metal binding protein |
| Biological source | Bacillus subtilis |
| Total number of polymer chains | 2 |
| Total formula weight | 83523.88 |
| Authors | Kubiak, X.,Polsinelli, I.,Chavas, L.M.G.,Legrand, P.,Fyfe, C.D.,Benjdia, A.,Berteau, O. (deposition date: 2022-07-25, release date: 2024-01-10, Last modification date: 2024-03-13) |
| Primary citation | Kubiak, X.,Polsinelli, I.,Chavas, L.M.G.,Fyfe, C.D.,Guillot, A.,Fradale, L.,Brewee, C.,Grimaldi, S.,Gerbaud, G.,Thureau, A.,Legrand, P.,Berteau, O.,Benjdia, A. Structural and mechanistic basis for RiPP epimerization by a radical SAM enzyme. Nat.Chem.Biol., 20:382-391, 2024 Cited by PubMed 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. PubMed: 38158457DOI: 10.1038/s41589-023-01493-1 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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