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

FEBS Letters

Pötsch, Stephan⁴  Sahlin, Margareta¹  Langelier, Yves²  Gräslund, Astrid³  Lassmann, Günter⁴ 

[1] Max-Volmer-Institute of Biophysical and Physical Chemistry, Technical University of Berlin, D-10623 Berlin, Germany;Institut du Cancer de Montréal, Hôpital Notre-Dame, Montréal, Québec H2L 4M1, Canada;Department of Biophysics, Stockholm University, Arrhenius Laboratories, S-10691 Stockholm, Sweden;Max-Delbrück-Center of Molecular Medicine, Robert-Rössle-Str. 10, D-13122 Berlin, Germany

关键词: Ribonucleotide reductase;    p-Alkoxyphenol;    Kinetic;    DNA;    deoxyribonucleic acid;    DTT;    dithiothreitol;    EPR;    electron paramagnetic resonance;    HSV-2;    herpes simplex virus type 2;    I;    spin quantum number;    RR;    ribonucleotide reductase;   

DOI  :  10.1016/0014-5793(95)01082-P

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown