AbstractThe 21‐peptide amide antibiotic gallidermin is a potential therapeutic against acne disease. It belongs to the class of polycyclic lanthionine and α,β‐clidehydroamino 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 Oterminal 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 triffuoroethanol : 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 Å 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.