PMID: 698227Aug 23, 1978Paper

S-adenosylhomocysteine analogues as inhibitors of specific tRNA methylation

Biochimica Et Biophysica Acta
P S LeboyR T Borchardt

Abstract

Of 17 base- or amino acid-modified analogues of S-adenosylhomocysteine, six were found to produce at least 50% inhibition of the activity of an unfractionated tRNA methyltransferase extract at concentrations of 200 micron. The inhibitory effects of these six analogues on five purified rat liver tRNA methyltransferases were examined. The purified enzymes differed greatly in their sensitivity to the analogues. Ki values for the inhibitory analogues were determined for the three most highly purified methyltransferases. The kinetic analyses indicated that inhibition is competitive for nearly all enzyme/inhibitor combinations. The Ki values for good enzyme/inhibitor pairs were in the range of 0.11--2 micron. Each analogue appears to inhibit one methylation more strongly than others; e.g. the Ki values obtained for N6-methyl-S-adenosyl-L-homocysteine are approx. 0.4 micron for guanine-1 tRNA methyltransferase, 6 micron for adenine-1 tRNA methyltransferase and 100 micron for N2-guanine tRNA methyltransferase I. Structural features which are important for inhibitory activity are presence of a terminal amino group on the amino acid and the presence of adenosine rather than any other base. Ring nitrogens, a terminal carboxyl group and co...Continue Reading

References

Mar 29, 1978·Biochimica Et Biophysica Acta·J M GlickP S Leboy
Jan 1, 1976·Biochimie·F Nau
Oct 1, 1976·Journal of Medicinal Chemistry·M E Gnegy, F J Lotspeich
Mar 1, 1975·Canadian Journal of Biochemistry·R D Walker, J A Duerre
Sep 2, 1975·Biochemical and Biophysical Research Communications·J D FinkelsteinA M Pick
Apr 22, 1968·Biochimica Et Biophysica Acta·A M Kaye, P S Leboy
May 1, 1971·Analytical Biochemistry·F SalvatoreS K Shapiro
Nov 1, 1974·Nucleic Acids Research·J Kraus, M Staehelin

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Citations

Oct 11, 2015·Journal of Pharmaceutical Sciences·Katharine Barbara SchowenMichael S Wolfe
Nov 1, 1982·Archives of Biochemistry and Biophysics·G PaolellaF Salvatore
Apr 13, 1979·Biochemical and Biophysical Research Communications·J N Lapeyre, F F Becker

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