6T33

The unusual structure of Ruminococcin C1 antimicrobial peptide confers activity against clinical pathogens

Summary for 6T33

• Entry DOI: 10.2210/pdb6t33/pdb
• NMR Information: BMRB: 50027
• Descriptor: Ruminococcin C (1 entity in total)
• Functional Keywords: bacteriocin, ruminoccin, antibiotic, thioether bridge, antimicrobial protein
• Biological source: [Ruminococcus] gnavus E1
• Total number of polymer chains: 1
• Total formula weight: 4333.76

Authors

Chiumento, S.,Roblin, C.,Bornet, O.,Nouailler, M.,Muller, C.,Basset, C.,Kieffer-Jaquinod, S.,Coute, Y.,Torelli, S.,Le Pape, L.,Shunemann, V.,Jeannot, K.,Nicoletti, C.,Iranzo, O.,Maresca, M.,Giardina, T.,Fons, M.,Devillard, E.,Perrier, J.,Atta, M.,Guerlesquin, F.,Lafond, M.,Duarte, V. (deposition date: 2019-10-10, release date: 2020-08-12, Last modification date: 2024-06-19)

Primary citation

Roblin, C.,Chiumento, S.,Bornet, O.,Nouailler, M.,Muller, C.S.,Jeannot, K.,Basset, C.,Kieffer-Jaquinod, S.,Coute, Y.,Torelli, S.,Le Pape, L.,Schunemann, V.,Olleik, H.,De La Villeon, B.,Sockeel, P.,Di Pasquale, E.,Nicoletti, C.,Vidal, N.,Poljak, L.,Iranzo, O.,Giardina, T.,Fons, M.,Devillard, E.,Polard, P.,Maresca, M.,Perrier, J.,Atta, M.,Guerlesquin, F.,Lafond, M.,Duarte, V.
The unusual structure of Ruminococcin C1 antimicrobial peptide confers clinical properties.
Proc.Natl.Acad.Sci.USA, 117:19168-19177, 2020

PubMed Abstract: The emergence of superbugs developing resistance to antibiotics and the resurgence of microbial infections have led scientists to start an antimicrobial arms race. In this context, we have previously identified an active RiPP, the Ruminococcin C1, naturally produced by E1, a symbiont of the healthy human intestinal microbiota. This RiPP, subclassified as a sactipeptide, requires the host digestive system to become active against pathogenic Clostridia and multidrug-resistant strains. Here we report its unique compact structure on the basis of four intramolecular thioether bridges with reversed stereochemistry introduced posttranslationally by a specific radical-SAM sactisynthase. This structure confers to the Ruminococcin C1 important clinical properties including stability to digestive conditions and physicochemical treatments, a higher affinity for bacteria than simulated intestinal epithelium, a valuable activity at therapeutic doses on a range of clinical pathogens, mediated by energy resources disruption, and finally safety for human gut tissues.

PubMed: 32719135
DOI: 10.1073/pnas.2004045117

Experimental method

SOLUTION NMR