Structural Basis for the Catalytic Mechanism of DncV, Bacterial Homolog of Cyclic GMP-AMP Synthase

Structure. 2015 May 5;23(5):843-850. doi: 10.1016/j.str.2015.01.023. Epub 2015 Apr 9.


Cyclic dinucleotides (CDNs) play key roles as second messengers and signaling molecules in bacteria and metazoans. The newly identified dinucleotide cyclase in Vibrio cholerae (DncV) produces three different CDNs containing two 3'-5' phosphodiester bonds, and its predominant product is cyclic GMP-AMP, whereas mammalian cyclic GMP-AMP synthase (cGAS) produces only cyclic GMP-AMP containing mixed 2'-5' phosphodiester bonds. We report the crystal structures of V. cholerae and Escherichia coli DncV in complex with various nucleotides in the pre-reaction states. The high-resolution structures revealed that DncV preferably recognizes ATP and GTP as acceptor and donor nucleotides, respectively, in the first nucleotidyl transfer reaction. Considering the recently reported intermediate structures, our pre-reaction state structures provide the precise mechanism of 3'-5' linked cyclic AMP-GMP production in bacteria. A comparison with cGAS in the pre-reaction states suggests that the orientation of the acceptor nucleotide primarily determines the distinct linkage specificities between DncV and cGAS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Catalytic Domain
  • Crystallography, X-Ray
  • Cyclic AMP / metabolism*
  • Cyclic GMP / metabolism*
  • Escherichia coli / chemistry
  • Escherichia coli / enzymology*
  • Guanosine Triphosphate / metabolism
  • Models, Molecular
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Vibrio cholerae / chemistry
  • Vibrio cholerae / enzymology*


  • Bacterial Proteins
  • Guanosine Triphosphate
  • Adenosine Triphosphate
  • Cyclic AMP
  • Cyclic GMP

Associated data

  • PDB/4XJ1
  • PDB/4XJ3
  • PDB/4XJ4
  • PDB/4XJ5
  • PDB/4XJ6