Reverse transcriptase: correlation of zinc content with activity

Proc Natl Acad Sci U S A. 1974 Dec;71(12):4892-6. doi: 10.1073/pnas.71.12.4892.

Abstract

Evidence is presented that DNA polymerase of avian myeloblastosis virus has an obligatory zinc requirement for activity. Previous studies indicate that the purified polymerase contains zinc in a stoichiometry of about 1 g-atom/mole. We now find that the enzyme-bound zinc is exchangeable with radioactive (65)Zn; after isoelectric focusing, the radioactive (65)Zn is coincident with polymerase activity. Dialysis of the (65)Zn-labeled polymerase against the chelator, 1,10-phenanthroline, results in a progressive loss of radioactive (65)Zn and polymerase activity. Thereupon, incubation of the inactivated enzyme with Zn(2+) fully restores activity. Thus, the DNA polymerase present in an oncogenic RNA virus, like animal DNA polymerases, can be rigorously classified as a zinc metalloenzyme. DNA polymerase of avian myeloblastosis virus is inactivated by 1,10-phenanthroline at a much faster rate than the bacterial and animal DNA polymerases that have been tested. It may, therefore, be possible to inactivate selectively DNA polymerases from animal tumor viruses by brief exposure to appropriate metal chelators.

MeSH terms

  • Avian Leukosis Virus / enzymology*
  • Avian Myeloblastosis Virus / enzymology*
  • Chelating Agents
  • Isoelectric Focusing
  • Phenanthrolines / pharmacology
  • RNA-Directed DNA Polymerase / metabolism*
  • Radioisotopes
  • Reverse Transcriptase Inhibitors
  • Zinc / metabolism*
  • Zinc Isotopes

Substances

  • Chelating Agents
  • Phenanthrolines
  • Radioisotopes
  • Reverse Transcriptase Inhibitors
  • Zinc Isotopes
  • RNA-Directed DNA Polymerase
  • Zinc