title: Novel reactivity of Fhit proteins: catalysts for fluorolysis of nucleoside 5'-phosphoramidates and nucleoside 5'-phosphosulfates to generate nucleoside 5'-phosphorofluoridates.
abstract: Fragile histidine triad (HIT) proteins (Fhits) occur in all eukaryotes but their function is largely unknown. Human Fhit is presumed to function as a tumour suppressor. Previously, we demonstrated that Fhits catalyse hydrolysis of not only dinucleoside triphosphates but also natural adenosine 5'-phosphoramidate (NH2-pA) and adenosine 5'-phosphosulfate (SO4-pA) as well as synthetic adenosine 5'-phosphorofluoridate (F-pA). In the present study, we describe an Fhit-catalysed displacement of the amino group of nucleoside 5'-phosphoramidates (NH2-pNs) or the sulfate moiety of nucleoside 5'-phosphosulfates (SO4-pNs) by fluoride anion. This results in transient accumulation of the corresponding nucleoside 5'-phosphorofluoridates (F-pNs). Substrate specificity and kinetic characterization of the fluorolytic reactions catalysed by the human Fhit and other examples of involvement of fluoride in the biochemistry of nucleotides are described. Among other HIT proteins, human histidine triad nucleotide-binding protein (Hint1) catalysed fluorolysis of NH2-pA 20 times and human Hint2 40 times more slowly than human Fhit.
authors.affiliation: *Department of Biochemistry and Biotechnology, Poznań University of Life Science, 11 Dojazd St., 60-632 Poznań, Poland.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Wojdyła-Mamoń
authors.affiliation: *Department of Biochemistry and Biotechnology, Poznań University of Life Science, 11 Dojazd St., 60-632 Poznań, Poland.
authors.forename: Jarosław
authors.initials: J
authors.lastname: Zimny
authors.affiliation: †Institute of Bioorganic Chemistry, Polish Academy of Science, 12-14 Noskowskiego St., 61-704 Poznań, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Romanowska
authors.affiliation: †Institute of Bioorganic Chemistry, Polish Academy of Science, 12-14 Noskowskiego St., 61-704 Poznań, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Kraszewski
authors.affiliation: †Institute of Bioorganic Chemistry, Polish Academy of Science, 12-14 Noskowskiego St., 61-704 Poznań, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Stawinski
authors.affiliation: ‡Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego At., 02-106 Warsaw, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Bieganowski
authors.affiliation: *Department of Biochemistry and Biotechnology, Poznań University of Life Science, 11 Dojazd St., 60-632 Poznań, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Guranowski
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000378:metabolism; D000250:Adenosine Phosphosulfate / Q000378:metabolism*; D002384:Catalysis; D005459:Fluorides / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D015394:Molecular Structure; D009363:Neoplasm Proteins / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism*; D013379:Substrate Specificity; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D000249:Adenosine Monophosphate; D000250:Adenosine Phosphosulfate; D005459:Fluorides; D009363:Neoplasm Proteins; D010710:Phosphates; D000099170:Bis(5'-adenosyl)triphosphatase; C012980:fluorophosphate; C015651:adenosine 5'-phosphoramidate