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Example sentences for: appppa
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AppppA is induced by heat shock in bacteria [ 36 ] and the induction of AppppA was thought to be a function of the heat-shock inducible LysU lysyl tRNA synthetase.
Human Fhit [ 14 ] and the S. cerevisiae Fhit homolog [ 13 ] , which was called Aph1 but is here termed Hnt2 under nomenclature aproved by the Saccharomyces Genome Database, cleave ApppA more readily while Aph1, the S. pombe homolog, cleaves AppppA more readily [ 20 ] . Consistent with the ApppA hydrolase activity of purified Fhit protein, most cancer cell lines that are Fhit negative at the protein level have higher levels of ApppA than cell lines that are Fhit positive [ 21 ] . Nonetheless, the actual concentrations of dinucleoside polyphosphates were submicromolar in every cell culture sample [ 21 ] and thus, under the reported culture conditions, the measured dinucleoside polyphosphates would not be expected to occupy the Fhit active site substantially [ 19 ] . Dinucleoside polyphosphate levels were measured in adenine-requiring S. cerevisiae strains before or after disruption of the Fhit-homologous HNT2 gene [ 13 ] and in adenine-requiring S. pombe strains as a function of disruption and overexpression of the Fhit-homologous aph1 gene [ 22 ] . Recently, it was observed that diadenosine polyphosphates undergo a divalent cation-dependent conformational change that might mediate their biosynthesis, catabolism or signaling properties [ 23 ] .
In the case of disruption of the Fhit and Hnt2-homologous aph1 gene in S. pombe , which encodes an enzyme relatively specific for a AppppA [ 20 ] , a 290-fold increase in AppppA concentration was observed [ 22 ] . Our data indicate that Hnt2 hydrolyzes ApppN and AppppN in vivo in budding yeast and that an intact adenine biosynthetic pathway is required for high-level synthesis and accumulation of adenylylated dinucleoside polyphosphates.
However, deletion of lysU had no effect on heat-shock inducible AppppA accumulation [ 37 ] . The KRS1 gene [ 38 ] encoding cytosolic lysyl tRNA synthetase was cloned into multicopy plasmid pRS423 [ 39 ] to generate plasmid pM1.
Covalent structures of AppppA ( 1 ) and compounds 6b and 12b are provided in Figure 1.
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