Protein radicals

Radicals play a diverse role in biology: they contribute to anything from normal anabolism to aging. Most radicals are highly reactive. Free radicals have little control over their reactivity once they are generated and readily attack a broad range of chemical targets, including sustained radical chain reactions. With few exceptions (such as inflammation response) free radicals are produced by external factors (UV light, chemical agents) or due loose control over metabolic pathways.

In prostaglandin H synthase, catalytic radical migrates from heme ring to Tyr₃₈₅ to substrate and back. Alternative radical sites are catalytically inactive.

In the area of radicals we are interested in another group of biological radicals that are generated intentionally for controlled use in radical catalysis. Radical enzymes is a rapidly growing group of enzymes that utilize highly oxidized catalytic species. Our group is particularly interested in catalytic radicals involved in energy transduction and synthesis.

Tyrosine radical in the active site of cytochrome c oxidase it located so close to paramegentic copper ion (Cu_B) that neither can be detected by EPR.

Catalytic radicals are usually produced at very specific protein sites nearby metal centers by temporary oxidation of amino acid side chain(s). Under physiological conditions protein radicals have oxidizing potentials comparable to that of metal-oxo species and are linked to metals both functionally and structurally.

Because of reactivity of radicals and their tendency to engage in side reactions, radical enzymes evolved for a strict control over accessibility and reactivity of transient radical species. Additional challenge arises from the ability of protein radicals to “migrate” over long distances unlike highly oxidized metal-oxo species. Some enzymes, such as prostaglandin H synthase and ribonucleotide reductase, have evolved to take advantage of radical mobility in their catalytic cycles.