Intratumoral pyrimidine nucleoside phosphorylase (pynpase) activity predicts a selective effect of adjuvant 5’-deoxy-5-fluorouridine (5’ dfur) on breast cancer

Breast Cancer ◽  
2000 ◽  
Vol 7 (1) ◽  
pp. 37-41 ◽  
Author(s):  
Yoshinobu Hata ◽  
Hiromasa Takahashi ◽  
Fumiaki Sasaki ◽  
Masami Ogita ◽  
Junichi Uchino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pyrimidine Nucleoside ◽  
Nucleoside Phosphorylase ◽  
Selective Effect ◽  
Pyrimidine Nucleoside Phosphorylase

scholarly journals The Peculiar Case of the Hyperthermostable Pyrimidine Nucleoside Phosphorylase from Thermus Thermophilus

2020 ◽  
Author(s):  
Felix Kaspar ◽  
Peter Neubauer ◽  
Anke Kurreck
Keyword(s):  
Thermus Thermophilus ◽  
Pyrimidine Nucleoside ◽  
Reaction Conditions ◽  
Nucleoside Phosphorylase ◽  
Pyrimidine Nucleosides ◽  
Low Concentrations ◽  
Pyrimidine Nucleoside Phosphorylase ◽  
Total Turnover ◽  
Nucleoside Phosphorylases ◽  
Peculiar Case

The poor solubility of many nucleoside and nucleobases in aqueous solution demands harsh reaction conditions (base, heat, cosolvent) in nucleoside phosphorylase-catalyzed processes to facilitate substrate loading beyond the low millimolar range. This, in turn, requires enzymes which withstand these conditions. Herein we report that the pyrimidine nucleoside phosphorylase from <i>Thermus thermophilus</i> is active over an exceptionally broad pH (4-10), temperature (up to 100 °C) and cosolvent space (up to 80% (v/v) non-aqueous medium) and displays tremendous stability under harsh reaction conditions with predicted total turnover numbers of more than 10<sup>6</sup> for various pyrimidine nucleosides. However, its use as a biocatalyst for preparative applications is critically limited due to its inhibition by nucleoside substrates at low concentrations, which is unprecedented among non-specific pyrimidine nucleoside phosphorylases.<br>

scholarly journals Characterization of pyrimidine nucleoside phosphorylase of Mycoplasma hyorhinis: implications for the clinical efficacy of nucleoside analogues

2012 ◽  
Vol 445 (1) ◽  
pp. 113-123 ◽  
Author(s):  
Johan Vande Voorde ◽  
Federico Gago ◽  
Kristof Vrancken ◽  
Sandra Liekens ◽  
Jan Balzarini
Keyword(s):  
Nucleoside Analogues ◽  
Kinetic Properties ◽  
Virus Infections ◽  
Pyrimidine Nucleoside ◽  
Mycoplasma Hyorhinis ◽  
Nucleoside Phosphorylase ◽  
Secondary Infections ◽  
Pyrimidine Nucleoside Phosphorylase ◽  
In Silico Analyses

In the present paper we demonstrate that the cytostatic and antiviral activity of pyrimidine nucleoside analogues is markedly decreased by a Mycoplasma hyorhinis infection and show that the phosphorolytic activity of the mycoplasmas is responsible for this. Since mycoplasmas are (i) an important cause of secondary infections in immunocompromised (e.g. HIV infected) patients and (ii) known to preferentially colonize tumour tissue in cancer patients, catabolic mycoplasma enzymes may compromise efficient chemotherapy of virus infections and cancer. In the genome of M. hyorhinis, a TP (thymidine phosphorylase) gene has been annotated. This gene was cloned, expressed in Escherichia coli and kinetically characterized. Whereas the mycoplasma TP efficiently catalyses the phosphorolysis of thymidine (Km=473 μM) and deoxyuridine (Km=578 μM), it prefers uridine (Km=92 μM) as a substrate. Our kinetic data and sequence analysis revealed that the annotated M. hyorhinis TP belongs to the NP (nucleoside phosphorylase)-II class PyNPs (pyrimidine NPs), and is distinct from the NP-II class TP and NP-I class UPs (uridine phosphorylases). M. hyorhinis PyNP also markedly differs from TP and UP in its substrate specificity towards therapeutic nucleoside analogues and susceptibility to clinically relevant drugs. Several kinetic properties of mycoplasma PyNP were explained by in silico analyses.

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