Cyclic di-GMP

Kibdelosporangium sp. AK-AA56 the PilZ domain protein PA4608 complex with cyclic di-GMP Vcc, VcN 251... 

Tal R., Wong H.C., Calhoon R., Gelfand D., Fear A.L., Volman G., Mayer R., Ross P., Amikam D., Weinhouse H., Cohen A., Sapir S., Ghana P., and Benziman M. 1998. Three cdg operons control cellular turnover of cyclic di-GMP in Acetobacter xylinum genetic organization and occurrence of conserved domains in isoenzymes. J Bacteriol 180 4416-4425. 

Riboswitches are ds-acting elements that regulate gene expression by affecting transcriptional termination or translational initiation in response to binding of an analyte. A number of riboswitches are described which are listed for inclusion without comment. These include adenine, " ATP, ° guanine, purine, preQi," " cyclic di-GMP, " theophylline, " SAM-I, " SAM-II, SAM-III, adeno-sylcobalamine, thiamine pyrophosphate, FMN, " lysine, " fluoride, T-box, M6, and the btuB riboswitch from E. coli. ... 

Of the RNA crystal structures reported there is the structure of the known RNA ligase ribozyme, an RNA aptamer binding to its bacterial protein target Hfq, myotonic dystrophy type 1 (DMl) RNA that showed internal UU loop structures, and the structure of the CUG helix from DMl, and a structure of the Fragile X syndrome repeating r(CGG) transcript/ " A number of crystal structures of riboswitches have been reported, including dG, cyclic-di-GMP, glycine, and M-box ° riboswitches. 

Current enzymatic syntheses of the widespread bacterial messenger molecule cyclic dinucleotide c-di-GMP (70) suffer from low production yields due to protein instability and strong product inhibition. Liang reported the overexpression of a standalone thermophilic diguanylate cyclase domain protein with enhance stability and decreased product inhibition profile due to site-specific mutation. " With this mutant, Liang produced hundreds of milligrams of c-di-GMP. 

By sequence similarity in combination with molecular modeling, the GGDEF domain has been suggested to confer nucleotide cyclization activity (Pei and Grishin 2001), but this function has to be experimentally proven. However, it is not very far fetched to speculate that the GGDEF domain might synthesize the cyclic nucleotide c-di-GMP, which has been identified as the allosteric activator for cellulose biosynthesis in G. xylinus (Ross et al. 1991). 

In the cellulose-producing bacterium Acetobacter xylinum, the phosphodiesterase A1 protein (AxPDEAl) functions to hydrolyze a potent allosteric activator of the bacterial cellulose synthase, the cyclic nucleotide [cyclic bis(3 —> 5 )diguanylic acid, or c-di-GMP] (17). xPDEAl was recently shown to contain an N-terminal regulatory heme-PAS domain that, when bound to O2, inhibits the C-terminal phosphodiesterase activity (10). Thus in cultures of this obligate aerobe, O2 is now thought to enhance the construction of a buoyant cellulose pellicle by the cells nearest to the media surface for possible use as a biofilm. The type of phosphodiesterase domain found in AxPDEAl, though not extensively studied, is widespread in Bacteria. 

Cirino G, Sorrentino R, d Emmanuele di Villa Bianca R, et al. Involvement of P3-adrenergic receptor activation via cyclic GMP- but not NO-dependent mechanisms in human corpus cavemosum function. Proc Natl Acad Sci USA 2003 100 5531-5536. 

The amount of nucleosides in cells is negligible also deoxyribonucleotides occur at insignificant levels in tissues. Ribonucleotides are important cellular components and occur as 5 -monophosphates, di-, tri-, and cyclic 3, 5 -phos-phates. Nucleoside phosphates function as energy carriers and serve as precursors for the synthesis of nucleic acids. Cyclic nucleotides (i.e., cyclic 3, 5 -AMP and cyclic-3, 5 -GMP) also play a role in metabolic regulation. 

The mechanism by which cheno (a di- -hydroxy-bile acid) induces diatrhea are probably related to the inhibition of water and electrolyte transport and to the activation of the adenylate cyclase cyclic AMP and guanylate cyclase cyclic GMP systems which would promote secretion of water and electrolytes. 

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