 | |
| Names | |
|---|---|
| IUPAC name O1,O7-Di(5′-deoxyadenosin-5′-yl) tetrahydrogen tetraphosphate | |
| Systematic IUPAC name O1,O7-Bis{[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl} tetrahydrogen tetraphosphate | |
| Other names Diadenosine tetraphosphate; 5',5'''-Diadenosine tetraphosphate; AppppA | |
| Identifiers | |
3D model (JSmol) | |
| ChEBI | |
| ChEMBL | |
| ChemSpider | |
| KEGG | |
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| Properties | |
| C20H28N10O19P4 | |
| Molar mass | 836.390 g·mol−1 |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Diadenosine tetraphosphate orAp4A is a putativealarmone, ubiquitous in nature being common to everything frombacteria tohumans. It is made up of two adenosines joined together by a 5′-5′ linked chain of four phosphates. Adenosine polyphosphates are capable of inducing multiplephysiological effects.[1]
Ap4A can be created by a non-canonical activity of the Lysyl-tRNA synthetase (LysRS). This function of LysRS is activated by the phosphorylation of LysRS on serine 207, its subsequent dissociation from the multi-synthetase complex (MSC).[2] The molecule's role as a second messenger has recently been discovered in TheLysRS-Ap4A-MITF signaling pathway.[3] Ap4A binds to the MITF-HINT1 inhibitory complex, specifically to the moleculehistidine triad nucleotide–binding protein 1(HINT1), releasing the Microphthalmia-associated transcription factor (MITF) and causing an increase in the transcription of its target genes.[4] Ap4A also positively regulates the activity of the transcription factorUSF2 through a similar molecular mechanism to that of MITF.[5]
It has also been shown, that Ap4A plays a role in the functionality ofdendritic cells (DCs). An increase in the intracellular amount Improves their motility and antigen presenting ability through alterations insmall GTPases present in the cells. This was discovered by creating mice deficient in the enzymeNUDT2, which serves as an Ap4Ahydrolase and thus controls the levels of Ap4A in the cell.[6] Ap4A, however, has also been shown to causeapoptosis in several cell lines through an unknown mechanism, the degradation of Ap4A was necessary for the process as hydrolysis-resistant analogues of the molecule showed no apoptotic activity.[7]
In E. Coli, Ap4A has been shown to function as an alarmone, as the intracellular concentration of the molecule increases upon heat stress.[8] Ap4A can also be incorporated into RNA as a5' Cap along with other dinucleoside polyphosphates. It serves as a substrate for theRNA polymerase and the intracellular levels of these capped RNAs increase upon stress, suggesting that the cap adds a level of stability to theRNA.[9]
Myxococcus xanthus is a type ofGram-negative bacteria, andM. xanthus lysyl-tRNA synthetase (LysS) is an enzyme from the bacteria that synthesizes diadenosine tetraphosphates (Ap4A) whenadenosine triphosphate (ATP) is present. Diadenosine pentaphosphate (Ap5A) is synthesized from Ap4A with ATP.[10]
