Nature Communications (Dec 2017)

Inhibition of D-Ala:D-Ala ligase through a phosphorylated form of the antibiotic D-cycloserine

  • Sarah Batson,
  • Cesira de Chiara,
  • Vita Majce,
  • Adrian J. Lloyd,
  • Stanislav Gobec,
  • Dean Rea,
  • Vilmos Fülöp,
  • Christopher W. Thoroughgood,
  • Katie J. Simmons,
  • Christopher G. Dowson,
  • Colin W. G. Fishwick,
  • Luiz Pedro S. de Carvalho,
  • David I. Roper

DOI
https://doi.org/10.1038/s41467-017-02118-7
Journal volume & issue
Vol. 8, no. 1
pp. 1 – 7

Abstract

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The antibiotic D-cycloserine (DCS) targets the peptidoglycan biosynthesis enzyme D-Ala-D-Ala ligase (Ddl). Here the authors reveal the DCS inhibitory mechanism by determining the structure of E. coli DdlB with a phosphorylated DCS molecule in the active site that formed in crystallo and mimics the D-alanyl phosphate intermediate.