9G05

Structure of MadB, a class I dehydrates from Clostridium maddingley, in complex with its substrate

9G05 の概要

• エントリーDOI: 10.2210/pdb9g05/pdb
• EMDBエントリー: 50910 50911
• 分子名称: Thiopeptide-type bacteriocin biosynthesis domain containing protein, Lantibiotic, gallidermin/nisin family (2 entities in total)
• 機能のキーワード: lanthipeptides, dehydratases, cryo-em structure, class i lantibiotic, biosynthetic protein
• 由来する生物種: Clostridium sp. Maddingley MBC34-26; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 257942.59

構造登録者

Knospe, C.V.,Ortiz, J.,Reiners, J.,Kedrov, A.,Gerten, C.,Smits, S.H.J.,Schmitt, L. (登録日: 2024-07-07, 公開日: 2025-07-16)

主引用文献

Knospe, C.V.,Ortiz, J.,Reiners, J.,Kedrov, A.,Gertzen, C.G.W.,Smits, S.H.J.,Schmitt, L.
Structural insights into the substrate binding mechanism of the class I dehydratase MadB.
Commun Biol, 8:1032-1032, 2025

PubMed Abstract: In the battle against antimicrobial resistance, lantibiotics have emerged as promising new sources for antimicrobial drugs. Their exceptional stability is due to characteristic modifications termed (methyl-)lanthionine rings. Genome mining efforts have identified hundreds of lantibiotics by detecting gene operons, so-called biosynthetic gene clusters (BGC), which encode cysteine-rich peptides (30-50 amino acids in size) and enzymes responsible for dehydration and cyclization, catalyzing the post-translational ring formation. One such identified, class I lantibiotic is maddinglicin from Clostridium maddingley. Here, we present single particle cryo-EM structures of the dehydratase MadB in both, its apo-state and in complex with a leader peptide of maddinglicin, revealing a distinct conformational change upon substrate binding. Small-angle X-ray scattering studies elucidate the substrate binding site for the C-terminal part of maddinglicin. Furthermore, a substrate specificity analysis was performed highlighting a critical stretch of amino acids within the maddinglicin leader sequence that is crucial for binding. Here, we provide molecular insights into the conformational changes, principles of substrate recognition and ligand:protein stoichiometry of a class I lantibiotic dehydratase.

PubMed: 40634635
DOI: 10.1038/s42003-025-08454-5

実験手法

ELECTRON MICROSCOPY (3.13 Å)