Disease relevance of guanosine pentaphosphate

• In Escherichia coli, amino acid starvation triggers the rapid synthesis of two guanosine polyphosphates, pppGpp and ppGpp (the 3'-pyrophosphates of GTP and GDP, respectively) [1].
• Borrelia burgdorferi rel is responsible for generation of guanosine-3'-diphosphate-5'-triphosphate and growth control [2].
• The stringent response is a mechanism by which bacteria adapt to nutritional deficiencies through the production of the guanine nucleotides ppGpp and pppGpp, produced by the RelA enzyme [3].
• Accumulation of ppGpp and pppGpp during nitrogen deprivation of the cyanophyte Anabaena cylindrica [4].
• Partial amino acid deprivation of Bacillus subtilis, which evokes the stringent response, initiates sporulation not because the highly phosphorylated guanine nucleotides guanosine-5'-diphosphate-3'-diphosphate (ppGpp) and guanosine-5'-triphosphate-3'-diphosphate (pppGpp) increase but because GTP decreases [5].

High impact information on guanosine pentaphosphate

• Phosphorylation of ppGpp to guanosine 5'-triphosphate,3'-diphosphate (pppGpp) prior to degradation was not necessary [6].
• The ability of pppGpp-5'-phosphohydrolase to hydrolyze pppGpp, pppGp, and pppGpNp, but not pppG and pppGpN, indicates that pppGpp-5'-phosphohydrolase is rather nonspecific toward the 3'-OH substitutions of the substrates although a free, unsubstituted phosphate group at the 3'-OH position is essential [7].
• The different mutants were reconstituted with programmed 70 S(DeltaL11) ribosomes and tested for their ability to stimulate stringent factor in a sensitive in vitro pppGpp synthesis assay [8].
• The global transcriptional regulator (p)ppGpp (guanosine-3'-diphosphate-5'-triphosphate and guanosine-3',5'-bisphosphate, collectively) produced by the relA and spoT genes in Escherichia coli allows bacteria to adapt to different environmental stresses [2].
• The absence of relA abolished the production of ppGpp and pppGpp under conditions of amino acid starvation [3].

Chemical compound and disease context of guanosine pentaphosphate

• Guanosine 5'-diphosphate 3'-diphosphate (ppGpp) and guanosine 5'-triphosphate 3'-diphosphate (pppGpp) were detected in formic acid extracts of air-exposed culutres of Bacteroides thetaiotaomicron [9].
• Purine nucleotide pyrophosphotransferase from Streptomyces morookaensis, capable of synthesizing pppApp and pppGpp [10].
• A spo T stringent strain of Escherichia coli rapidly accumulates guanosine 5'-triphosphate,3'-diphosphate (pppGpp) immediately after the onset of isoleucine starvation [11].

Biological context of guanosine pentaphosphate

• The k(cat) for hydrolysis, however, is reduced 2-fold and K(m) for pppGpp increased 2-fold from basal levels in the presence of the Rel(Mtb) activating complex [12].
• The data were consistent with the interpretation that ppGpp is a positive effector of his operon expression, whereas pppGpp is not an essential effector [13].
• Neither ppGpp nor pppGpp appeared to influence gnd gene expression [13].
• Kinetics of accumulation and degradation of ppGpp and pppGpp were analysed in spoT+ and spoT strains of Escherichia coli [14].
• This activates the rel gene product which forms ppGpp and pppGpp from GTP and ATP [15].

Anatomical context of guanosine pentaphosphate

• Neither pppGpp, ppGp, nor pGpp was effective as inhibitor in this cell-free system [16].

Associations of guanosine pentaphosphate with other chemical compounds

• The accumulation of ppGpp and pppGpp in the presence of charged tRNA provided by chloramphenicol treatment suggests that the signal for the synthesis of unusual nucleotides is an inhibition of the binding of tRNA (charged or uncharged) to the acceptor site of the ribosome [15].

Gene context of guanosine pentaphosphate

• This result indicates that spoT also participates in pppGpp degradation [17].
• Two independent mutants were isolated which resemble relaxed (relA) mutants of Escherichia coli; they continue to synthesize RNA and accumulate neither ppGpp nor pppGpp when deprived of the required amino acid [18].
• While d-pppGpp closely resembled pppGpp in its very low activity with EF-G, d-pppGp was somewhat more active [19].
• Ribosomes carrying either EF-Tu or EF-G are active in binding the stringent factor; however, they are inactive in synthesizing guanosine 5'-triphosphate 3'-diphosphate (pppGpp) and guanosine 5'-diphosphate 3'-diphosphate (ppGpp) [20].
• These results strongly support the identity of GPSI as a bifunctional enzyme capable of both pppGpp synthesis and polynucleotide phosphorylase activities [21].

Analytical, diagnostic and therapeutic context of guanosine pentaphosphate

• Structure-based sequence analysis suggests that the pppGpp synthetase active site is located in the first core domain [22].

References