Selective inhibition of the 3'-to-5' exonuclease activity associated with Epstein-Barr virus DNA polymerase by ribonucleoside 5'-monophosphates. 1992

T Tsurumi
Laboratory of Virology, Nagoya University School of Medicine, Japan.

Epstein-Barr virus (EBV) DNA polymerase possesses a proofreading 3'-to-5' exonuclease activity (Tsurumi, T. (1991) Virology 182, 376-381). The 3'-to-5' exonuclease activity can be selectively inhibited by ribonucleoside 5'-monophosphates, while no inhibition of the DNA polymerase activity can be observed even when the template/primer concentrations are rate-limiting. Deoxynucleoside monophosphates except 5'dGMP have almost no effect on the exonuclease activity. Of the four ribonucleoside monophosphates, 5'GMP is the most potent (62% inhibition at 5 mM). The kinetic study shows that 5'-GMP inhibits the exonuclease activity competitively with respect to DNA template/primer. During DNA polymerization process the EBV DNA polymerase catalyzes the DNA-dependent conversion of complementary deoxynucleoside triphosphate to monophosphate form. With poly(dT).oligo(rA) as a template primer, selective inhibition of the exonuclease activity by 5'-GMP results in a decrease in the amount of free dAMP generated which is complementary to the template DNA, suggesting the functional relationship between the editing exonuclease activity and the chain elongation activity of the EBV DNA polymerase molecule.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D004854 Herpesvirus 4, Human The type species of LYMPHOCRYPTOVIRUS, subfamily GAMMAHERPESVIRINAE, infecting B-cells in humans. It is thought to be the causative agent of INFECTIOUS MONONUCLEOSIS and is strongly associated with oral hairy leukoplakia (LEUKOPLAKIA, HAIRY;), BURKITT LYMPHOMA; and other malignancies. Burkitt Herpesvirus,Burkitt Lymphoma Virus,E-B Virus,EBV,Epstein-Barr Virus,Human Herpesvirus 4,Infectious Mononucleosis Virus,Burkitt's Lymphoma Virus,HHV-4,Herpesvirus 4 (gamma), Human,Burkitts Lymphoma Virus,E B Virus,E-B Viruses,Epstein Barr Virus,Herpesvirus, Burkitt,Infectious Mononucleosis Viruses,Lymphoma Virus, Burkitt,Mononucleosis Virus, Infectious,Mononucleosis Viruses, Infectious
D004926 Escherichia coli A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc. Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli
D005092 Exonucleases Enzymes that catalyze the release of mononucleotides by the hydrolysis of the terminal bond of deoxyribonucleotide or ribonucleotide chains. Exonuclease,3'-5'-Exonuclease,3'-5'-Exonucleases,5'-3'-Exonuclease,5'-3'-Exonucleases,3' 5' Exonuclease,3' 5' Exonucleases,5' 3' Exonuclease,5' 3' Exonucleases
D012265 Ribonucleotides Nucleotides in which the purine or pyrimidine base is combined with ribose. (Dorland, 28th ed) Ribonucleoside Phosphates,Ribonucleotide,Phosphates, Ribonucleoside
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D019384 Nucleic Acid Synthesis Inhibitors Compounds that inhibit cell production of DNA or RNA. DNA Polymerase Inhibitor,DNA Synthesis Inhibitor,DNA Synthesis Inhibitors,Nucleic Acid Synthesis Inhibitor,RNA Synthesis Inhibitor,RNA Synthesis Inhibitors,DNA Polymerase Inhibitors,Inhibitors, DNA Synthesis,Inhibitors, Nucleic Acid Synthesis,Inhibitors, RNA Synthesis,Inhibitor, DNA Polymerase,Inhibitor, DNA Synthesis,Inhibitor, RNA Synthesis,Inhibitors, DNA Polymerase,Polymerase Inhibitor, DNA,Polymerase Inhibitors, DNA,Synthesis Inhibitor, DNA,Synthesis Inhibitor, RNA,Synthesis Inhibitors, DNA,Synthesis Inhibitors, RNA

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