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

Angew Chem Int Ed Engl. 2017 Dec 22;56(52):16546-16549. doi: 10.1002/anie.201709240. Epub 2017 Nov 30.

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.

Keywords: C55-P; bacterial cell wall; calcium-dependent antibiotics; crystal structure; laspartomycin c.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Calcium / chemistry
  • Crystallography, X-Ray
  • Lipopeptides / chemistry*
  • Molecular Conformation
  • Peptides, Cyclic / chemistry*
  • Streptomyces / chemistry
  • Streptomyces / metabolism

Substances

  • Anti-Bacterial Agents
  • Lipopeptides
  • Peptides, Cyclic
  • laspartomycin C
  • Calcium