Words similar to diadenosine
Example sentences for: diadenosine
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The human FHIT gene, located at the chromosome 3 fragile site FRA3B, is inactivated early in the development of many tumors [ 1 ] . Murine Fhit is also located at a fragile site [ 2 3 ] and mice heterozygous for disruption of Fhit , given low intragastric doses of the mutagen N-nitrosomethylbenzylamine, develop stomach and sebaceous tumors [ 4 ] that can be prevented by viral Fhit expression [ 5 ] . Fhit, a dimer of 147 amino acid subunits, is a member of the histidine triad (HIT) superfamily of nucleotide hydrolases and transferases [ 6 7 ] . Members of the Hint branch of the HIT superfamily are found in all forms of life [ 8 ] . The S. cerevisiae Hint homolog, Hnt1, and rabbit Hint possess adenosine monophosphoramidase activity that functions in yeast to positively regulate function of Kin28, Ccl1 and Tfb3, which constitute the kinase component of general transcription factor TFIIH [ 9 ] . A new Hint related protein, Aprataxin, is mutated in individuals with ataxia with oculomotor apraxia [ 10 11 ] and has a yeast homolog termed Hnt3 [ 9 ] . Members of the Fhit branch of the HIT superfamily have been found in fungi [ 12 13 ] , animals [ 2 14 15 ] and plants [ 7 ] and hydrolyze diadenosine tetraphosphate, diadenosine triphosphate and other 5'-5"'-dinucleoside polyphosphates.
Because diadenosine polyphosphate levels vary with time in culture, generating a higher or lower range of values in independently conducted experiments, we did not average values obtained in separate experiments.
An added benefit of these constructions is the availability of yeast strains that possess high levels of dinucleoside polyphosphates and at the same time express a mutant Fhit-homologous protein, because these are conditions which have been postulated to constitute the signaling form of Fhit [ 16 ] . Finally, using controlled genotypes we revisited conditions that lead to increased accumulation of dinucleoside polyphosphates [ 24 25 26 27 28 29 30 31 32 33 ] . Recognizing that hnt2 deletion is a pathological condition, we were particular interested in identifying conditions that lead to accumulation of such compounds in cells that contain a functional HNT2 gene, rather than simply identifying conditions that produce diadenosine polyphosphate accumulation in the absence of Hnt2.
When diadenosine 5',5"'-( P 1, P 2-methylene- P 3-thio)- P 1, P 3-triphosphate [ 17 ] was crystallized with wild-type and mutant Fhit, the α-phosphorothioate group was found in the mutant but not wild-type active site, suggesting that α-phosphorothioate inhibitors may be slow substrates [ 12 ] . Similarly, Frey and co-workers found that Fhit slowly cleaves both R p and S p stereoisomers of γ-( m -nitrobenzyl)-adenosine 5'- O -(l-thiotriphosphate) with modest and similar beneficial effects on K m as compared to the corresponding phosphate [ 13 ] .
Larger increases in AppppN concentrations have been seen with disruption of Apa1 and Apa2, the diadenosine tetraphosphate phosphorylases in S. cerevisiae [ 34 35 ] , indicating that they have a more significant role in controlling AppppN levels than does Hnt2.