Reduction of the tyrosyl radical and the iron center in protein R2 of ribonucleotide reductase from mouse, herpes simplex virus and E. coli by p-alkoxyphenols.
The rate of reduction of the tyrosyl radical in the small subunit of ribonucleotide reductase (protein R2) from E. coli, mouse, and herpes simplex virus (HSV-2) by a series of p-alkoxyphenols with different alkyl chains, have been studied by stopped-flow UV-vis and stopped-flow EPR spectroscopy. The reduction and release of iron in R2 by the inhibitors was followed using bathophenanthroline as chelator of Fe2+. p-Alkoxyphenols reduce the mouse R2 tyrosyl radical 1-2 orders of magnitude faster than the HSV-2 and E. coli radical. In contrast to E. coli, the iron center in R2 from mouse and HSV-2 is reduced by the inhibitors. For mouse R2, the rate of reduction of the tyrosyl radical increases in parallel with increasing alkyl chain length of the inhibitor, an observation which may be important for the design of new antiproliferative drugs.
Pötsch
S
S
Max-Delbrück-Center of Molecular Medicine, Berlin, Germany.
Sahlin
M
M
Langelier
Y
Y
Gräslund
A
A
Lassmann
G
G
D000818:Animals; D004578:Electron Spin Resonance Spectroscopy; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology*; D018258:Herpesvirus 2, Human / Q000201:enzymology*; D007501:Iron / Q000378:metabolism*; D051379:Mice; D009603:Nitroso Compounds / Q000737:chemistry; D010084:Oxidation-Reduction; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D014443:Tyrosine / Q000187:drug effects* / Q000378:metabolism
D004791:Enzyme Inhibitors; D009603:Nitroso Compounds; D010636:Phenols; C001259:Fremy's salt; D014443:Tyrosine; D007501:Iron; D012264:Ribonucleotide Reductases