Mechanism of ribonucleotide reductase from Herpes simplex virus type 1. Evidence for 3' carbon-hydrogen bond cleavage and inactivation by nucleotide analogs
Isotope effects of 2.5, 2.1, and 1.0 were measured on the conversion of (3'-3H)ADP, (3'-H)UDP, and (5-3H) UDP to the corresponding 2'-deoxynucleotides by herpes simplex virus type 1 ribonucleotide reductase. These results indicate that the reduction of either purine or pyrimidine nucleotides requires cleavage of the 3' carbon-hydrogen bond of the substrate. The substrate analogs 2'-chloro-2'-deoxyuridine 5'-diphosphate (ClUDP), 2'-deoxy-2'-fluorouridine 5'-diphosphate, and 2'-azido-2'-deoxyuridine 5'-diphosphate were time-dependent inactivators of the herpes simplex virus type 1 ribonucleotide reductase. Incubation of (3'-3H)ClUDP with the enzyme was accompanied by time-dependent release of 3H to the solvent. Reaction of (beta-32P)ClUDP with the reductase resulted in the production of inorganic pyrophosphate. These results are consistent with the enzyme-mediated cleavage of the 3' carbon-hydrogen bond of ClUDP and the subsequent conversion of the nucleotide to 2-methylene-3(2H)furanone, as previously reported with the Escherichia coli ribonucleotide reductase.
- Research Organization:
- Univ. of Wisconsin, Madison
- OSTI ID:
- 5738977
- Journal Information:
- J. Biol. Chem.; (United States), Vol. 8
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
PURINES
INACTIVATION
PYRIMIDINES
TRITIUM
ISOTOPE EFFECTS
HERPES SIMPLEX
NUCLEOTIDES
OXIDOREDUCTASES
AROMATICS
AZAARENES
AZINES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
DISEASES
ENZYMES
HETEROCYCLIC COMPOUNDS
HYDROGEN ISOTOPES
INFECTIOUS DISEASES
ISOTOPES
LIGHT NUCLEI
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RADIOISOTOPES
SKIN DISEASES
VIRAL DISEASES
YEARS LIVING RADIOISOTOPES
560111* - Radiation Effects on Biochemicals- In Vitro- (-1987)