Structure of the lipopeptide antibiotic tsushimycin.
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.
Bunkóczi
Gábor
G
Lehrstuhl für Strukturchemie, Georg-August Universität, Tammannstrasse 4, 37077 Göttingen, Germany. gabor.bunkoczi@sgc.ox.ac.uk
Vértesy
László
L
Sheldrick
George M
GM
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002118:Calcium / Q000737:chemistry; D018360:Crystallography, X-Ray; D005231:Fatty Acids, Unsaturated / Q000737:chemistry; D055666:Lipopeptides; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D010456:Peptides, Cyclic; D011487:Protein Conformation; D020836:Protein Structure, Quaternary
D000900:Anti-Bacterial Agents; D005231:Fatty Acids, Unsaturated; D055666:Lipopeptides; D010455:Peptides; D010456:Peptides, Cyclic; C031299:tsushimycin; D002118:Calcium