Structure of the lipopeptide antibiotic tsushimycin

✍ Scribed by Bunkóczi, Gábor ;Vértesy, László ;Sheldrick, George M.

• Publisher: International Union of Crystallography
• Year: 2005
• Tongue: English
• Weight: 289 KB
• Volume: 61
• Category: Article
• ISSN: 0907-4449
• DOI: 10.1107/s0907444905017270

✦ Synopsis

The amphomycin derivative tsushimycin has been crystallized and its structure determined at 1.0 A 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.