Solution structures of the lantibiotics duramycin B and C.
The solution structures of the lantibiotics duramycin B in H2O/2H2O (9:1) and duramycin C in (2H3)acetonitrile/H2O (1:1) have been determined by NMR followed by distance-geometry and restrained-molecular-mechanics calculations. The constitution and location of three thioether bridges and a lysinoalanine ring system could be established by unambiguously assigned NOE contacts between the bridging side chains. Model building based on NMR constraints resulted in a U-shaped topology of the tetracyclic 19-peptides with a turn around Pro9 and a kink along a virtual line from residues 5 to 13. This clamp-like conformation is stabilized by the thioether bridges and is additionally supported by an antiparallel beta-strand-like structure of the N-termini and C-termini and the inherent amphiphilicity of duramycin-type lantibiotics. The duramycins B and C differ mainly in the relative mobilities of their rings A, C and D. Duramycin B is closely related to cinnamycin with an exchange of Phe10 to leucine, whereas duramycin C differs from duramycin B by three conserved and two non-conserved amino-acid exchanges.
Institut für Organische Chemie, Eberhard-Karls-Universität Tübingen, Germany.
N
N
Zimmermann
S
S
Freund
A
A
Fredenhagen
G
G
Jung
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D023181:Antimicrobial Cationic Peptides; D001430:Bacteriocins; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D012996:Solutions
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001430:Bacteriocins; D010455:Peptides; D012996:Solutions; C066795:duramycin B; C066796:duramycin C