6VE9

Solution NMR structure of enterococcal cytolysin S (CylLS") produced by Enterococcus faecalis

Summary for 6VE9

• Entry DOI: 10.2210/pdb6ve9/pdb
• NMR Information: BMRB: 30702
• Descriptor: enterococcal cytolysin S (1 entity in total)
• Functional Keywords: lanthipeptide, cytolysin, cyclic peptide, posttranslational modification, toxin
• Biological source: Enterococcus faecalis
• Total number of polymer chains: 1
• Total formula weight: 2037.47

Authors

Bobeica, S.C.,van der Donk, W.A.,Zhu, L.,Tang, W. (deposition date: 2019-12-30, release date: 2020-07-08, Last modification date: 2023-06-14)

Primary citation

Bobeica, S.C.,Zhu, L.,Acedo, J.Z.,Tang, W.,van der Donk, W.A.
Structural determinants of macrocyclization in substrate-controlled lanthipeptide biosynthetic pathways.
Chem Sci, 11:12854-12870, 2020

PubMed Abstract: Lanthipeptides are characterized by thioether crosslinks formed by post-translational modifications. The cyclization process that favors a single ring pattern over many other possible ring patterns has been the topic of much speculation. Recent studies suggest that for some systems the cyclization pattern and stereochemistry is determined not by the enzyme, but by the sequence of the precursor peptide. However, the factors that govern the outcome of the cyclization process are not understood. This study presents the three-dimensional structures of seven lanthipeptides determined by nuclear magnetic resonance spectroscopy, including five prochlorosins and the two peptides that make up cytolysin, a virulence factor produced by that is directly linked to human disease. These peptides were chosen because their substrate sequence determines either the ring pattern (prochlorosins) or the stereochemistry of cyclization (cytolysins). We present the structures of prochlorosins 1.1, 2.1, 2.8, 2.10 and 2.11, the first three-dimensional structures of prochlorosins. Our findings provide insights into the molecular determinants of cyclization as well as why some prochlorosins may be better starting points for library generation than others. The structures of the large and small subunits of the enterococcal cytolysin show that these peptides have long helical stretches, a rare observation for lanthipeptides characterized to date. These helices may explain their pore forming activity and suggest that the small subunit may recognize a molecular target followed by recruitment of the large subunit to span the membrane.

PubMed: 34094481
DOI: 10.1039/d0sc01651a

Experimental method

SOLUTION NMR