Structure and catalytic mechanism of heterodisulfide reductase from methanogenic archaea

点击翻译按钮获取中文摘要

Heterodisulfide reductase from methanogenic archaea is an ironsulfur protein that can catalyze the reversible reduction of the heterodisulfide (CoM-S-S-CoB) of the methanogenic thiolcoenzymes, coenzyme M and coenzyme B. Iron-sulfur clusters can only perform one-electron transfer reactions. Thus the central problem that needs to be addressed in heterodisulfide reductase is how a one-electron donor can carry out the concerted twoelectron reduction of a disulfide. It is likely that radical type intermediates are formed during this process, for example a thiyl radical formed by the initial one-electron reduction of the disulfide. Our working hypothesis is that such a thiyl radical might be stabilized by an iron-sulfur cluster in the catalytic centre of the enzyme. Recent investigations have identified a paramagnetic centre in heterodisulfide reductase with EPR properties not common to known iron-sulfur clusters. The g-values and the redox properties of this paramagnetic centre are specifically altered by incubation of the enzyme with its substrate. It therefore might be an intermediate in the catalytic cycle. These findings are an important basis for further investigations. The objectives of this project are the characterization of the active-site of this enzyme and the identification of the intermediates of the catalytic cycle.