Cyclic di-AMP

Cyclic di-AMP
Names
IUPAC name
(1S,6R,8R,9R,10S,15R,17R,18R)-8,17-Bis(6-aminopurin-9-yl)-3,12-dihydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3λ5,12λ5-diphosphatricyclo[13.3.0.06,10]octadecane-9,18-diol
Other names
3',5'-cyclic di-AMP; c-di-AMP; c-di-adenosine monophosphate
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
UNII
  • InChI=1S/C20H24N10O12P2/c21-15-9-17(25-3-23-15)29(5-27-9)19-11(31)13-7(39-19)1-37-43(33,34)42-14-8(2-38-44(35,36)41-13)40-20(12(14)32)30-6-28-10-16(22)24-4-26-18(10)30/h3-8,11-14,19-20,31-32H,1-2H2,(H,33,34)(H,35,36)(H2,21,23,25)(H2,22,24,26)/t7-,8-,11-,12-,13-,14-,19-,20-/m1/s1
    Key: PDXMFTWFFKBFIN-XPWFQUROSA-N
  • C1[C@@H]2[C@H]([C@H]([C@@H](O2)N3C=NC4=C(N=CN=C43)N)O)OP(=O)(OC[C@@H]5[C@H]([C@H]([C@@H](O5)N6C=NC7=C(N=CN=C76)N)O)OP(=O)(O1)O)O
Properties
C20H24N10O12P2
Molar mass 658.418 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Cyclic di-AMP (also called c-di-AMP and c-di-adenosine monophosphate) is a second messenger used in signal transduction in bacteria and archaea.[1][2][3] It is present in many Gram-positive bacteria, some Gram-negative species, and archaea of the phylum Euryarchaeota.[2][3]

Cyclic di-AMP crystal structure

It is one of many ubiquitous nucleotide second messengers including cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), guanosine pentaphosphate ((p)ppGpp), and cyclic di-GMP (c-di-GMP). c-di-AMP is a signaling nucleotide used in signaling pathways that trigger outputs by using receptor or target proteins to sense c-di-AMP concentrations in the cell.

In bacteria, cyclic di-AMP has been implicated in the control of growth, cell wall homeostasis, bacterial biofilm formation and virulence gene expression, heat and osmotic stress regulation and responses, sporulation, potassium transport, lysis, and antibiotic resistance.[2][4]

In humans, cyclic di-AMP has been implicated in the control of innate immune response and antiviral response against pathogens. The dinucleotide is also produced by numerous human pathogens, prompting the exploration of numerous c-di-AMP-regulating pathways both in humans and in bacteria.

  1. ^ Dey B, Dey RJ, Cheung LS, Pokkali S, Guo H, Lee JH, Bishai WR (April 2015). "A bacterial cyclic dinucleotide activates the cytosolic surveillance pathway and mediates innate resistance to tuberculosis". Nature Medicine. 21 (4): 401–6. doi:10.1038/nm.3813. PMC 4390473. PMID 25730264.
  2. ^ a b c Corrigan RM, Gründling A (August 2013). "Cyclic di-AMP: another second messenger enters the fray". Nature Reviews. Microbiology. 11 (8): 513–24. doi:10.1038/nrmicro3069. hdl:10044/1/19649. PMID 23812326. S2CID 29830881.
  3. ^ a b Braun F, Thomalla L, van der Does C, Quax TE, Allers T, Kaever V, Albers SV (September 2019). "Cyclic nucleotides in archaea: Cyclic di-AMP in the archaeon Haloferax volcanii and its putative role". MicrobiologyOpen. 8 (9): e00829. doi:10.1002/mbo3.829. PMC 6741144. PMID 30884174.
  4. ^ Zhu Y, Pham TH, Nhiep TH, Vu NM, Marcellin E, Chakrabortti A, et al. (March 2016). "Cyclic-di-AMP synthesis by the diadenylate cyclase CdaA is modulated by the peptidoglycan biosynthesis enzyme GlmM in Lactococcus lactis". Molecular Microbiology. 99 (6): 1015–27. doi:10.1111/mmi.13281. hdl:10453/41116. PMID 26585449. S2CID 24427957.