The 21-peptide
amide antibiotic gallidermin is a potential therapeutic against
acne disease. It belongs to the class of polycyclic
lanthionine and alpha,beta-didehydroamino
acids containing
polypeptides, which were named "
lantibiotics." The structural gene of the recently elucidated
lantibiotic gallidermin encodes a precursor
peptide containing Ser, Thr, and Cys residues in the C-terminal prolantibiotic part, and an unusually hydrophilic
leader peptide. The ribosomally synthesized pregallidermin is posttranslationally modified and processed to a complex
peptide antibiotic with four
sulfide rings and two unsaturated residues. The complete
solution structure of
gallidermin was determined in
trifluoroethanol: water (95:5) and
dimethylsulfoxide by two-dimensional 1H-nmr at 500 MHz, using a combination of double quantum filtered correlated spectroscopy, homonuclear Hartman-Hahn, and nuclear Overhauser enhancement spectroscopy experiments. Using a total number of 152 distance constraints from NOEs and 14 torsional constraints, derived from coupling constants, we obtained a screwlike
solution structure of
gallidermin. Restrained molecular dynamics simulations yielded a set of five converging structures with an atomic rms difference of 1.7 A for the backbone atoms, not dependent on the starting structure. The spatial structure model is in excellent agreement with the amphiphilic and channel-forming properties of
gallidermin on membranes and its tryptic cleavage at the exposed site between residues 13 and 14.