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

8AI5 の概要

• エントリーDOI: 10.2210/pdb8ai5/pdb
• 分子名称: Putative peptide biosynthesis protein YydG, Putative exported peptide YydF, IRON/SULFUR CLUSTER, ... (7 entities in total)
• 機能のキーワード: radical sam, metalloenzyme, iron-sulfur, ripp, metal binding protein
• 由来する生物種: Bacillus subtilis; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 85510.05

構造登録者

Polsinelli, I.,Fyfe, C.D.,Legrand, P.,Kubiak, X.,Chavas, L.M.G.,Berteau, O.,Benjdia, A. (登録日: 2022-07-25, 公開日: 2024-01-10, 最終更新日: 2024-03-13)

主引用文献

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

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: 38158457
DOI: 10.1038/s41589-023-01493-1

実験手法

X-RAY DIFFRACTION (2.15 Å)