A High-Resolution Crystal Structure that Reveals Molecular Details of Target Recognition by the Calcium-Dependent Lipopeptide Antibiotic Laspartomycin C

Abstract

The calcium-dependent antibiotics (CDAs) are an important emerging class of antibiotics. The crystal structure of the CDA laspartomycin C in complex with calcium and the ligand geranyl-phosphate at a resolution of 1.28 Å is reported. This is the first crystal structure of a CDA bound to its bacterial target. The structure is also the first to be reported for an antibiotic that binds the essential bacterial phospholipid undecaprenyl phosphate (C55-P). These structural insights are of great value in the design of antibiotics capable of exploiting this unique bacterial target.