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. 2020 Feb 25;48(6):2807–2829. doi: 10.1093/nar/gkaa112

Table 1.

Comparison of c-di-AMP- and c-di-GMP-mediated signaling

c-di-GMP c-di-AMP
Discovery year 1987 2008
Chemical properties
Structural formula C20H24N10O14P2 C20H24N10O12P2
Molecular weight 690.4 Da 658.4 Da
PDB structure code C2E (95 structures) 2BA (33 structures)
Oligomeric structure Monomer, dimer (tetramer) Monomer (dimer)
Intracellular levelsa 0.1–10 μM 0.5–18.8 μM
Turnover enzymes: gene and domain namesb, structures
Synthetase(cyclase) : DgcA, AdrA
GGDEF domain (PF00990, PDB: 1W25b)
DisA, CdaA, CdaS, CdaM, CdaZ
DisA_N (DAC) domain (PF02457, PDB: 3C1Y)
Hydrolase class I YhjH, YkuI, BlrP1
EAL domain (PF00563, PDB: 2R6O)
GdpP/PdeA, DhhP, DHH and DHHA1
domains (PF01388/PF02272, PDB: 5XSN)
Hydrolase class II RpfG, PmGH, TM0186
HD-GYP domain (COG2206, PDB: 4R8Z)
PgpH
HDc domain (PF01966, PDB: 4S1B)
Receptor types
Riboswitches Class I (PDB: 3IRW), Class II (PDB:3Q3Z) YdaO (PDB: 4QLN)
Bacterial proteinsa
Widespread c-di-NMP-binding domains PilZ domain (PF07238, PDB: 1YWU) RCK_C domain (PF02080, PDB: 4XTT)
MshEN domain (PDB: 5HTL) CBS domain pair (PDB: 5KS7)
Histidine kinases CckA, HATPase domain (PDB: 5IDM) KdpD, USP-like domain (PDB: 2R8R)
Transcriptional regulators BldD (PDB: 5KHD); FleQ (PDB: 5EXX) BusR (RCK_C domain); DarR (COG4977)
Eukaryotic proteins STING (PDB: 4EMT) STING (PDB: 6CFF)
DDX41 (PDB: 5GVR) RECON (PDB: 5UXF)
Phylogenetic distribution All bacterial phyla, Dictyostelium Most bacterial phyla, Euryarchaeota
Regulated processes Transcription, protein and polysaccharide secretion, motility, cell development, biofilm formation DNA repair, sporulation, K+ transport, osmotic homeostasis, central metabolism, biofilm formation

aCyclic di-AMP levels in wild-type cells have been reported to range from 0.49–0.96 μM in M. pneumoniae (33) and 1.7–5.1 μM in B. subtilis (4) to 18.8 μM in Synechococcus elongatus (72).

bOnly some examples are presented, see text and Table 2 for more details and references. The domain names are from the Pfam (5) and COG (6) databases, protein and RNA structures are from the PDB.