Novel reactivity of Fhit proteins: catalysts for fluorolysis of nucleoside 5'-phosphoramidates and nucleoside 5'-phosphosulfates to generate nucleoside 5'-phosphorofluoridates
| Autor: | Jarosław Zimny, Adam Kraszewski, Paweł Bieganowski, Andrzej Guranowski, Anna Maria Wojdyla-Mamon, Jacek Stawinski, Joanna Romanowska |
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| Rok vydání: | 2015 |
| Předmět: |
Stereochemistry
Biochemistry Catalysis Phosphates Substrate Specificity Hydrolysis Fluorides FHIT medicine Moiety Humans Nucleotide neoplasms Molecular Biology Histidine chemistry.chemical_classification Molecular Structure Chemistry Triad (anatomy) Cell Biology Adenosine Adenosine Monophosphate Acid Anhydride Hydrolases Adenosine Phosphosulfate Neoplasm Proteins Kinetics medicine.anatomical_structure Nucleoside medicine.drug |
| Zdroj: | The Biochemical journal. 468(2) |
| ISSN: | 1470-8728 |
| Popis: | 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. Abbreviations: Fhit, fragile histidine triad protein; F-pA, adenosine 5′-phosphorofluoridate; F-pN, nucleoside 5′-phosphorofluoridate; Hint, histidine triad nucleotide-binding protein; HIT, histidine triad; NH2-pA, adenosine 5′-phosphoramidate; NH2-pN, nucleoside 5′-phosphoramidate; pA, 5′-AMP; SO4-pA, adenosine 5′-phosphosulfate; SO4-pN, a nucleoside 5′-phosphosulfate |
| Databáze: | OpenAIRE |
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