9G04

Structure of MadB, a class I dehydrates from Clostridium maddingley in the apo state

Summary for 9G04

• Entry DOI: 10.2210/pdb9g04/pdb
• EMDB information: 50910
• Descriptor: Thiopeptide-type bacteriocin biosynthesis domain containing protein (1 entity in total)
• Functional Keywords: lanthipeptides, dehydratases, cryo-em structure, class i lantibiotic, biosynthetic protein
• Biological source: Clostridium sp. Maddingley MBC34-26
• Total number of polymer chains: 2
• Total formula weight: 246184.53

Authors

Knospe, C.V.,Ortiz, J.,Reiners, J.,Kedrov, A.,Gertzen, C.,Smits, S.H.J.,Schmitt, L. (deposition date: 2024-07-06, release date: 2025-07-16)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (2.7 Å)