Crystal structures of the c-di-AMP-synthesizing enzyme CdaA

J Biol Chem. 2019 Jul 5;294(27):10463-10470. doi: 10.1074/jbc.RA119.009246. Epub 2019 May 22.


Cyclic di-AMP (c-di-AMP) is the only second messenger known to be essential for bacterial growth. It has been found mainly in Gram-positive bacteria, including pathogenic bacteria like Listeria monocytogenes CdaA is the sole diadenylate cyclase in L. monocytogenes, making this enzyme an attractive target for the development of novel antibiotic compounds. Here we report crystal structures of CdaA from L. monocytogenes in the apo state, in the post-catalytic state with bound c-di-AMP and catalytic Co2+ ions, as well as in a complex with AMP. These structures reveal the flexibility of a tyrosine side chain involved in locking the adenine ring after ATP binding. The essential role of this tyrosine was confirmed by mutation to Ala, leading to drastic loss of enzymatic activity.

Keywords: X-ray crystallography; cyclic di-AMP (c-di-AMP); metal ion–protein interaction; prokaryotic signal transduction; second messenger.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Catalytic Domain
  • Cobalt / chemistry
  • Cobalt / metabolism
  • Crystallography, X-Ray
  • Dinucleoside Phosphates / chemistry
  • Dinucleoside Phosphates / metabolism
  • Ligands
  • Listeria monocytogenes / enzymology*
  • Molecular Dynamics Simulation
  • Mutagenesis, Site-Directed
  • Phosphorus-Oxygen Lyases / chemistry*
  • Phosphorus-Oxygen Lyases / genetics
  • Phosphorus-Oxygen Lyases / metabolism
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics


  • Bacterial Proteins
  • Dinucleoside Phosphates
  • Ligands
  • Recombinant Proteins
  • cyclic diadenosine phosphate
  • Cobalt
  • Phosphorus-Oxygen Lyases

Associated data

  • PDB/4RV7
  • PDB/6HVL
  • PDB/6HVM
  • PDB/6HVN