RNA-Dependent DNA Polymerase (Reverse Transcriptase) from Avian Myeloblastosis Virus: A Zinc Metalloenzyme
AUTOR(ES)
Auld, D. S.
RESUMO
RNA tumor viruses contain a characteristic RNA-dependent DNA polymerase (reverse transcriptase) which has been thought to be related to the induction of leukemia by this virus. A disturbance in a zinc-dependent enzyme system was first postulated to account for the demonstrated differences in zinc metabolism of normal and leukemic leukocytes [Vallee et al. in (1949) Acta Unio. Int. Contra Cancrum 6, 869 and (1950) Acta Unio. Int. Contra Cancrum 6, 1102]. In order to investigate the relationship between zinc and the initiation of leukemia in chickens by avian myeloblastosis virus, we have examined the metalloenzyme nature of its reverse transcriptase. The present data show that this protein is a zinc metalloenzyme demonstrating the postulated relationship between zinc and a leukemic process. Paucity of purified enzyme generated the design of a novel system of analysis incorporating microwave-induced emission spectrometry combined with gel exclusion chromatography. It provides precision, reproducibility, and remarkable limits of detection on μl samples containing 10-12 to 10-14 g-atoms of metal, and is thus orders of magnitude more sensitive than other methods. The chromatographic fraction with highest enzymatic activity contains 1.8 × 10-11 g-atoms of zinc per 1.6 μg of protein, corresponding to either 1.8 or 2.0 g-atoms of zinc per mole of enzyme for a molecular weight previously determined either as 1.6 or 1.8 × 105. Copper, iron and manganese are absent, i.e., at or below the limits of detection, 10-13 to 10-14 g-atoms. Agents known to chelate zinc inhibit the enzyme, while their nonchelating isomers do not. The data underline the participation of zinc in nucleic acid metabolism and bear importantly upon the lesions that accompany leukemia and zinc deficiency.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=388392Documentos Relacionados
- Specific binding of tryptophan transfer RNA to avian myeloblastosis virus RNA-dependent DNA polymerase (reverse transcriptase).
- Inhibition of RNA-Dependent DNA Polymerase of Avian Myeloblastosis Virus by Pyran Copolymer
- RNA-dependent DNA polymerase activity of RNA tumor virus. VI. Processive mode of action of avian myeloblastosis virus polymerase.
- Region of immunoglobulin light-chain mRNA transcribed into complementary DNA by RNA-dependent DNA polymerase of avian myeloblastosis virus.
- Relationship Between RNA-directed DNA Polymerase (Reverse Transcriptase) from Human Acute Leukemic Blood Cells and Primate Type-C Viruses