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Mechanism of ribonucleotide reductase from Herpes simplex virus type 1. Evidence for 3' carbon-hydrogen bond cleavage and inactivation by nucleotide analogs

Journal Article · · J. Biol. Chem.; (United States)
OSTI ID:5738977
; ;

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), Journal Name: J. Biol. Chem.; (United States) Vol. 8; ISSN JBCHA
Country of Publication:
United States
Language:
English

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Related Subjects

560111* -- Radiation Effects on Biochemicals-- In Vitro-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AROMATICS
AZAARENES
AZINES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
DISEASES
ENZYMES
HERPES SIMPLEX
HETEROCYCLIC COMPOUNDS
HYDROGEN ISOTOPES
INACTIVATION
INFECTIOUS DISEASES
ISOTOPE EFFECTS
ISOTOPES
LIGHT NUCLEI
NUCLEI
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXIDOREDUCTASES
PURINES
PYRIMIDINES
RADIOISOTOPES
SKIN DISEASES
TRITIUM
VIRAL DISEASES
YEARS LIVING RADIOISOTOPES