8BYK

The structure of MadC from Clostridium maddingley reveals new insights into class I lanthipeptide cyclases

Summary for 8BYK

• Entry DOI: 10.2210/pdb8byk/pdb
• Descriptor: Lanthionine synthetase C-like protein, ZINC ION, SODIUM ION, ... (7 entities in total)
• Functional Keywords: cyclase, lantibiotic, biosynthetic, biosynthetic protein
• Biological source: Clostridium
• Total number of polymer chains: 1
• Total formula weight: 51380.86

Authors

Knospe, C.V.,Kamel, M.,Spitz, O.,Hoeppner, A.,Galle, S.,Reiners, J.,Kedrov, A.,Smits, S.H.,Schmitt, L. (deposition date: 2022-12-13, release date: 2023-02-22, Last modification date: 2024-06-19)

Primary citation

Knospe, C.V.,Kamel, M.,Spitz, O.,Hoeppner, A.,Galle, S.,Reiners, J.,Kedrov, A.,Smits, S.H.J.,Schmitt, L.
The structure of MadC from Clostridium maddingley reveals new insights into class I lanthipeptide cyclases.
Front Microbiol, 13:1057217-1057217, 2022

PubMed Abstract: The rapid emergence of microbial multi-resistance against antibiotics has led to intense search for alternatives. One of these alternatives are ribosomally synthesized and post-translationally modified peptides (RiPPs), especially lantibiotics. They are active in a low nanomolar range and their high stability is due to the presence of characteristic (methyl-) lanthionine rings, which makes them promising candidates as bacteriocides. However, innate resistance against lantibiotics exists in nature, emphasizing the need for artificial or tailor-made lantibiotics. Obviously, such an approach requires an in-depth mechanistic understanding of the modification enzymes, which catalyze the formation of (methyl-)lanthionine rings. Here, we determined the structure of a class I cyclase (MadC), involved in the modification of maddinglicin (MadA) X-ray crystallography at a resolution of 1.7 Å, revealing new insights about the structural composition of the catalytical site. These structural features and substrate binding were analyzed by mutational analyses of the leader peptide as well as of the cyclase, shedding light into the mode of action of MadC.

PubMed: 36741885
DOI: 10.3389/fmicb.2022.1057217

Experimental method

X-RAY DIFFRACTION (1.7 Å)