Diguanylate cyclases are characterized by the conserved amino acid sequence motifs “GGDEF” (Gly-Gly-Asp-Glu-Phe) or “GGEEF” (Gly-Gly-Glu-Glu-Phe), which constitute the domain of the DGC active site.

[9] In Pseudomonas fluorescens DGC WspR activity is hypothesized to be partially responsible for the wrinkly spreader (WS) phenotype.

The active form of diguanylate cyclase PleD localizes to the stalked pole of differentiating C. crescentus cells.

[4][14] Cyclic di-GMP binds to interface between the DGC and D2 domains stabilizing the open structure and preventing catalysis.

[4] Though the exact catalytic mechanism has not been resolved, it is hypothesized that the dimerized structure of PleD facilitates interaction of the two GTP molecules within the DGC active site for cyclization.

A proposed mechanism by Chan et al. indicates that the 3'-OH group of the GTP is deprotonated by a glutamic acid residue (E370) to allow for intermolecular nucleophilic attack of the α-phosphate.