# The World of Cyclic Dinucleotides in Bacterial Behavior
## 3 Cyclic Dinucleotide Receptors
3’-5’ c-di-GMP structures found in degenerate EAL domains are colored in cyan (PDBID: 3 HV8, 4F3H, 4F48, 3 PJT, 3 PJU), in riboswitches are colored in green (PDBID: 3Q3Z, 3 MXH, 3 MUT, 3 MUR, 3 MUM, 3 IRW, 4 YB0, 3 IWN), in STING proteins are colored in blue (PDBID: 4 EF4, 4 EMT, 6 RM0, 6S86, 4F9G, 4F5D, 4F5Y, 6A04, 5 CFL, 5 CFP), in PilZ domains are colored in pink (dimeric c-di-GMP: PDBID: 4 ZMN, 5 EUH, 3 BRE, 3J5C, 1W25, 2 WB4, 2V0N, 3 TVK, 3I5A, 3 IGM, 4 URG, 4 URS. Trimeric c-di-GMP, PDBID: 4 XRN), in the active site of GGDEF domains (monomeric c-di-GMP, PDBID: 4 RT1), and in the GGDEF I-site (dimeric c-di-GMP, PDBID: 5 EY, 5 EJ1, 5 EJZ, 4P00, 4P02, 5 KGO, 5 EJL, 5 VX6, 5Y4R, 5 XLY, 2L74, 4 RT0, 5Y6F, 5Y6G) are colored in purple, in the T2 SSE_N domain is colored in brown (PDBID: 5 HTL), in the HATPase_c (CA) domain is colored in blue (PDBID: 5 IDM), in the REC domain is colored in yellow (PDBID: 3 KLO), and in the Sigma54_activat domain is colored in orange (PDBID: 5 EXX). The unusual c-di-GMP oligomeric states found in one GGDEF active site is colored in pink and brown (PDBID: 3 QYY), and in the C-terminal domain of BldD is colored in yellow (PDBID: 4 OAZ); (**C**) different conformations for 3’-5’ c-di-AMP found in different protein binding pockets and riboswitches shown as a superposition between them. 3’-5’ c-di-AMP structures found in riboswitches are colored in green (PDBID: 4 QK8, 4 QK9, 4W92, 4W90, 4 QLM, 4 QLN, 4 QKA), in TrkA_C domains are colored in brown (PDBID: 4 YS2, 4 YP1, 5F29), in Cyclic-di-AMP receptor domains are colored in yellow (PDBID: 4 WK1, 4D3H, 4 RWW, 4 RLE), in a STING protein is colored in dark blue (PDBID: 6 IYF),  
in an Aldo-keto reductase domain is colored in light blue (PDBID: 5 UXF), in a Pyruvate carboxylase domain is colored in red (PDBID: 5 VZ0), in the active site of cGAS is colored in dark green (PDBID: 3C1Y), and in a CBS domain is colored in orange (PDBID: 5 KS7); (**D**) 3'-5' cGAMP is found in _intermediate_ and _closed_ conformations in the ligand binding pocket of riboswitches, colored in green (PDBID: 4 YAZ and 4 YB1), and in a STING protein, colored in blue (PDBID: 5 CFM). 2'-3' cGAMP is found in a _closed_ conformation in the ligand binding pocket of STING proteins, colored in blue (PDBID: 6 NT7, 6 NT8, 5 CFQ, 4 LDH, 4 LOJ, 5 GRM, 4 KSY, and 6A06). The dinucleotides can assume different conformations in the binding site of different receptors that can be described in relation to the base and the ribose conformations. The ribose ring can assume three different configurations, C3'-endo, C2'-endo, or C2'-exo. When taking into account receptor structures in complex with cyclic dinucleotides (Table 1), more than 80% of the ligands have the two pentose rings in C3'-endo, almost 15% have one of the pentoses in C3'-endo and the other in C2'-endo and only one structure has the two pentoses in C2'-exo configuration (Figure 8A). Furthermore, the base can assume a _syn_ or _anti_ conformation in relation to the pentose by the N-glycosic bond, and only one of the structures, the FilmX EAL domain from _Xanthomonas citri_ (PDBID: 4 FOK) [168] has one of the base at the _syn_ conformation, which is the less stable state of the molecule. The conformation C3'-endo/C3'-endo is the more representative for the c-di-GMP and c-di-AMP molecules, while cGAMP is preferentially in C3'-endo/C2'-endo conformation (Figure 8A). The overall conformation of the ligand can be classified in three conformations with respect to the base proximity: 1--_closed_ conformation (shaped as a horseshoe) is when the two base rings are face-to-face; 2--_open_ conformation is when the two base rings are far from each other in an elongated conformation and; 3--_intermediate_ conformation (shaped as a boat) is when the bases are not in the _closed_ conformation or in the _open_ conformation (Figure 8A).