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Specific inhibition of herpesvirus ribonucleotide reductase by a nonapeptide derived from the carboxy terminus of subunit 2

Nature volume 321, pages 441443 (22 May 1986) | Download Citation

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Abstract

Ribonucleotide reductase, an essential enzyme for the synthesis of deoxyribonucleotides, is formed by the association of two non-identical subunits in almost all prokaryotic and eukaryotic cells1. The same model probably holds for the herpes simplex virus (HSV)-encoded ribonucleotide reductase2–6; two polypeptides of relative molecular mass 136,000 (136K; H1) and 40K (H2) (referred to elsewhere as RR1 and RR2; see for example, Dutia et al.26) have been associated with the viral enzyme by both genetic7,8 and immunological9–11 studies. Furthermore, DNA sequence analyses have shown significant stretches of amino-acid homology between these viral polypeptides and those of, respectively, subunit 1 (ref. 12) and subunit 2 (ref. 13) of the Escherichia coli and mammalian enzymes. To assess the involvement of the 40K polypeptide in reductase activity, we synthesized a nonapeptide corresponding to the sequence of its carboxy terminus with the intention of raising neutralizing antibodies specific for the viral activity (E.A.C. et al., in preparation). We report here the unexpected finding that the nonapeptide itself specifically inhibits the HSV ribonucleotide reductase activity in a reversible, non-competitive manner, and we suggest that it does this by impairment of the correct association of the two subunits. This phenomenon emphasizes the potential usefulness of synthetic peptides in probing critical sites involved in macromolecular interactions.

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Affiliations

  1. Institut du Cancer de Montréal, Centre Hospitalier Notre-Dame, 1560 rue Sherbrooke est, Montréal, Québec, Canada H2L 4M1

    • E. A. Cohen
    •  & Y. Langelier
  2. Laboratoire de Neuroendocrinologie, Centre de Recherche de l'Hôpital Notre-Dame, Centre Hospitalier Notre-Dame, 1560 rue Sherbrooke est, Montréal, Québec, Canada H2L 4M1

    • P. Gaudreau
    •  & P. Brazeau

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https://doi.org/10.1038/321441a0

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