9GMC

Crystal structure of the complex formed between the radical SAM protein ChlB and the R3A mutant of ChlA

9GMC の概要

• エントリーDOI: 10.2210/pdb9gmc/pdb
• 分子名称: ChlB radical SAM domain, ChlA R3A mutant, IRON/SULFUR CLUSTER, ... (6 entities in total)
• 機能のキーワード: radical sam protein ribosomally synthesised and post-translationally modified peptides iron sulfur clusters peptide binding protein, oxidoreductase
• 由来する生物種: Fischerella; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 106482.48

構造登録者

de la Mora, E.,Ruel, J.,Usclat, A.,Martin, L.,Amara, P.,Morinaka, B.,Nicolet, Y. (登録日: 2024-08-28, 公開日: 2025-06-25)

主引用文献

Ruel, J.,Nguyen, T.Q.N.,Morishita, Y.,Usclat, A.,Martin, L.,Amara, P.,Kieffer-Jaquinod, S.,Stefanoiu, M.C.,de la Mora, E.,Morinaka, B.I.,Nicolet, Y.
Peptide Recognition and Mechanism of the Radical S -Adenosyl-l-methionine Multiple Cyclophane Synthase ChlB.
J.Am.Chem.Soc., 147:16850-16863, 2025

PubMed Abstract: Ribosomally synthesized and post-translationally modified peptides (RiPPs) represent a valuable class of natural products, often featuring macrocyclization, which enhances stability and rigidity to achieve specific conformations, frequently underlying antibiotic activity. ChlB is a metalloenzyme with two catalytic domains─a radical -adenosyl-l-methionine (SAM) domain and an α-ketoglutarate-dependent oxygenase─that work in tandem to sequentially form three cyclophanes and introduce three hydroxyl groups into its substrate peptide, ChlA. Here, we present the crystal structure of the radical SAM domain of ChlB in complex with ChlA, revealing the mechanism underlying cyclophane formation. These structures also elucidate how the leader sequence of ChlA interacts with ChlB. By combining structural, in vitro, and in vivo approaches, we determined the precise sequence of the three cyclophane formations, interspersed with hydroxylation events. Our findings demonstrate a back-and-forth movement of the core peptide between the radical SAM domain and the oxygenase domain, which drives the stepwise modification process, leading to the fully modified peptide.

PubMed: 40354606
DOI: 10.1021/jacs.4c16004

実験手法

X-RAY DIFFRACTION (1.77 Å)