Example sentences for: diadenosine

How can you use “diadenosine” in a sentence? Here are some example sentences to help you improve your vocabulary:

  • On the basis that Fhit binds diadenosine polyphosphates with one AMP group buried and the other adenosine solvent-exposed in a specific conformation [ 12 ] , effective tri and tetrapodal inhibitors such as 12b, 13b and HC(ADP) 3 [ 15 ] may exist in solution predominantly in a conformation that resembles Fhit-bound AppppA.

  • 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.

  • 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 ] .

  • 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 ] .

  • 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.


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