Structure of the lipopeptide antibiotic tsushimycin

The amphomycin derivative tsushimycin has been crystallized and its structure determined at 1.0 Å resolution. The asymmetric unit contains 12 molecules and with 1300 independent atoms this structure is one of the largest solved using ab initio direct methods. The antibiotic is comprised of a cyclodecapeptide core, an exocyclic amino acid and a fatty-acid residue. Its backbone adopts a saddle-like conformation that is stabilized by a Ca²⁺ ion bound within the peptide ring and accounts for the Ca²⁺-dependence of this antibiotic class. Additional Ca²⁺ ions link the antibiotic molecules to dimers that enclose an empty space resembling a binding cleft. The dimers possess a large hydrophobic surface capable of interacting with the bacterial cell membrane. The antibiotic daptomycin may exhibit a similar conformation, as the amino-acid sequence is conserved at positions involved in Ca²⁺ binding.