<i>Anabaena flos-aquae</i> and other cyanobacteria possess diadenosine 5′,5‴-P1,P4-tetraphosphate (Ap4A) phosphorylase activity

McLennan, Alexander G.; Mayers, Elaine; Adams, David G.

doi:10.1042/bj3200795

Cited by 14 publications

(5 citation statements)

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“…Instead, two isoenzymes catalysing Ap 4 A phosphorolysis have been uncovered (see [12, 13]). Recently, the same activity was found in cyanobacteria in addition to the symmetrical hydrolase activity [69, 70]. Reaction catalysed by Ap 4 A phosphorylase is described as Ap 4 A+P i ⇔ATP+ADP.…”

Section: Ap N a Metabolismmentioning

confidence: 62%

Diadenosine oligophosphates (Ap_nA), a novel class of signalling molecules?

et al. 1998

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The diadenosine oligophosphates (Ap n A) were discovered in the mid-sixties in the course of studies on aminoacyltRNA synthetases (aaRS). Now, more than 30 years later, about 300 papers have been published around these substances in attempt to decipher their role in cells. Recently, Ap n A have emerged as intracellular and extracellular signalling molecules implicated in the maintenance and regulation of vital cellular functions and become considered as second messengers. Great variety of physiological and pathological effects in mammalian cells was found to be associated with alterations of Ap n A levels (n from 2 to 6) and Ap Q A/Ap R A ratio. Cell differentiation and apoptosis have substantial and opposite effects on Ap Q A/Ap R A ratio in cultured cells. A human Ap Q A hydrolase, Fhit, appeared to be involved in protection of cells against tumourigenesis. Ap Q A is synthesised by mammalian u synthetase (TrpRS) which in contrast to most other aaRS is unable to synthesise Ap R A and is an interferon-inducible protein. Moreover, Ap Q A appeared to be a preferred substrate for 2-5A synthetase, also interferoninducible, priming the synthesis of 2P adenylated derivatives of Ap Q A, which in turn may serve as substrates of Fhit. Tumour suppressor activity of Fhit is assumed to be associated with involvement of the FhitWAp Q A complex in cytokine signalling pathway(s) controlling cell proliferation. The Ap n A family is potentially a novel class of signal-transducing molecules whose functions are yet to be determined.z 1998 Federation of European Biochemical Societies.

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Section: Ap N a Metabolismmentioning

confidence: 62%

Diadenosine oligophosphates (Ap_nA), a novel class of signalling molecules?

et al. 1998

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“…Physarum polycephalum Ap 4 A → ADP + ADP Garrison et al, 1982 "Asymmetrical" Nudix Ap 4 A hydrolase Animals (e.g., Nudt2), plants (e.g., AtNUDT25), proteobacteria (RppH/NudH/IalA/YgdP), mycobacteria (MutT1) Guranowski, 2000;McLennan, 2006;Kraszewska, 2008;Arif et al, 2017 Ap 4 A phosphorylase Guranowski and Blanquet, 1985;McLennan et al, 1994McLennan et al, , 1996Hou et al, 2013;Honda et al, 2015 HIT family hydrolases S. cerevisiae (Aph), H. sapiens (FHIT)…”

Section: Enzymementioning

confidence: 99%

“…They are similar to the GalT proteins of the HIT family, which have a typical HXHXQφφ motif. Cyanobacteria and mycobacteria also have Ap 4 A phosphorylases ( McLennan et al, 1996 ; Mori et al, 2010 ; Honda et al, 2015 ). The enzyme from M. tuberculosis is unusual in that it has a proper HIT motif (HφHφHφφ) more similar to the HIT family hydrolases than other Ap 4 A phosphorylases, but other amino acid changes in the active site may account for its phosphorylase activity ( Mori et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Re-evaluation of Diadenosine Tetraphosphate (Ap4A) From a Stress Metabolite to Bona Fide Secondary Messenger

Ferguson

McLennan

Urbaniak

et al. 2020

Front. Mol. Biosci.

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Cellular homeostasis requires adaption to environmental stress. In response to various environmental and genotoxic stresses, all cells produce dinucleoside polyphosphates (Np n Ns), the best studied of which is diadenosine tetraphosphate (Ap 4 A). Despite intensive investigation, the precise biological roles of these molecules have remained elusive. However, recent studies have elucidated distinct and specific signaling mechanisms for these nucleotides in prokaryotes and eukaryotes. This review summarizes these key discoveries and describes the mechanisms of Ap 4 A and Ap 4 N synthesis, the mediators of the cellular responses to increased intracellular levels of these molecules and the hydrolytic mechanisms required to maintain low levels in the absence of stress. The intracellular responses to dinucleotide accumulation are evaluated in the context of the “friend” and “foe” scenarios. The “friend (or alarmone) hypothesis” suggests that Ap n N act as bona fide secondary messengers mediating responses to stress. In contrast, the “foe” hypothesis proposes that Ap n N and other Np n N are produced by non-canonical enzymatic synthesis as a result of physiological and environmental stress in critically damaged cells but do not actively regulate mitigating signaling pathways. In addition, we will discuss potential target proteins, and critically assess new evidence supporting roles for Ap n N in the regulation of gene expression, immune responses, DNA replication and DNA repair. The recent advances in the field have generated great interest as they have for the first time revealed some of the molecular mechanisms that mediate cellular responses to Ap n N. Finally, areas for future research are discussed with possible but unproven roles for intracellular Ap n N to encourage further research into the signaling networks that are regulated by these nucleotides.

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“…(ii) An Ap 4 A (asymmetrical) pyrophosphohydrolase (Ap 4 A→AMP+ATP, EC 3.6.1.17) has been described for Schizosaccharomyces pombe and all higher eukaryotes (invertebrates, vertebrates and plants) studied so far. (iii) A phosphorolytic cleavage occurs in yeast [4], protozoa [5]and cyanobacteria [6]by a reversible acting Ap 4 A phosphorylase (Ap 4 A+Pi↔ADP+ATP; EC 2.7.7.53).…”

Section: Introductionmentioning

confidence: 99%

Cloning and expression of a new cDNA from monocotyledonous plants coding for a diadenosine 5′,5′′′‐P¹,P⁴‐tetraphosphate hydrolase from barley (Hordeum vulgare)

et al. 1998

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From a cDNA library generated from mRNA of white leaf tissues of the ribosome‐deficient mutant ‘albostrians' of barley (Hordeum vulgare cv. Haisa) a cDNA was isolated carrying 54.2% identity to a recently published cDNA which codes for the diadenosine‐5′,5′′′‐P1,P4‐tetraphosphate (Ap4A) hydrolase of Lupinus angustifolius (Maksel et al. (1998) Biochem. J. 329, 313–319), and 69% identity to four partial peptide sequences of Ap4A hydrolase of tomato. Overexpression in Escherichia coli revealed a protein of about 19 kDa, which exhibited Ap4A hydrolase activity and cross‐reactivity with an antibody raised against a purified tomato Ap4A hydrolase (Feussner et al. (1996) Z. Naturforsch. 51c, 477–486). Expression studies showed an mRNA accumulation in all organs of a barley seedling. Possible functions of Ap4A hydrolase in plants will be discussed.

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Anabaena flos-aquae and other cyanobacteria possess diadenosine 5′,5‴-P1,P4-tetraphosphate (Ap4A) phosphorylase activity

Cited by 14 publications

References 50 publications

Diadenosine oligophosphates (Ap_nA), a novel class of signalling molecules?

Diadenosine oligophosphates (Ap_nA), a novel class of signalling molecules?

Re-evaluation of Diadenosine Tetraphosphate (Ap4A) From a Stress Metabolite to Bona Fide Secondary Messenger

Cloning and expression of a new cDNA from monocotyledonous plants coding for a diadenosine 5′,5′′′‐P¹,P⁴‐tetraphosphate hydrolase from barley (Hordeum vulgare)

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Anabaena flos-aquae and other cyanobacteria possess diadenosine 5′,5‴-P1,P4-tetraphosphate (Ap4A) phosphorylase activity

Cited by 14 publications

References 50 publications

Diadenosine oligophosphates (ApnA), a novel class of signalling molecules?

Diadenosine oligophosphates (ApnA), a novel class of signalling molecules?

Re-evaluation of Diadenosine Tetraphosphate (Ap4A) From a Stress Metabolite to Bona Fide Secondary Messenger

Cloning and expression of a new cDNA from monocotyledonous plants coding for a diadenosine 5′,5′′′‐P1,P4‐tetraphosphate hydrolase from barley (Hordeum vulgare)

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Diadenosine oligophosphates (Ap_nA), a novel class of signalling molecules?

Diadenosine oligophosphates (Ap_nA), a novel class of signalling molecules?

Cloning and expression of a new cDNA from monocotyledonous plants coding for a diadenosine 5′,5′′′‐P¹,P⁴‐tetraphosphate hydrolase from barley (Hordeum vulgare)