The Free Radical-Coupled Copper Active Site

The Free Radical-Coupled Copper Active Site 

The free radical-copper complex in active GAOX combines two distinct reactive sites to form a two-electron redox unit in the protein with new properties, different from those of the individual components. The 

---

VII. The Free Radical-Coupled Copper Active Site. 36... 

Whittaker, J. W., 1994, The free radical-coupled copper active site in galactose oxidase. Metal Ions in Biology, Editors Sigel, H. and Sigel, A., Marcel Dekker publishers, 30 3159 360. 

Whittaker, J. W. The Free Radical-Coupled Copper Active Site of Galactose Oxidase. In Metalloenzymes Involving Amino Acid Residue and Related Radicals Sigel, H. Sigel, A., Eds., Marcel Dekker New York, 1994, Vol. 30, pp 315-360. Knowles, P. F. Ito, N. Galactose Oxidase. In Perspectives in Bioinorganic Chemistry Jai Press London, 1994 Vol. 2, pp 207-244. 

Since both alcoholic oxidation and O2 reduction are two-electron processes, the catalytic reaction is conceptually equivalent to a transfer of the elements of dihydrogen between the two substrates. Biological hydrogen transfer generally involves specialized organic redox factors (e.g., flavins, nicotinamide, quinones), with well-characterized reaction mechanisms. Galactose oxidase does not contain any of these conventional redox factors and instead utilizes a very different type of active site, a free radical-coupled copper complex, to perform this chemistry. The new type of active site structure implies that the reaction follows a novel biochemical redox mechanisms based on free radicals and the two-electron reactivity of the metalloradical complex. 

GAO contains an unusual free radical-coupled copper catal3rtic motif in its active site, which acts as a radical center during the two-electron reaction (39). This reaction undergoes reduction and oxidation with alcohol and O2 in a ping-pong mechanism. In the first half-reaction, the alcohol is oxidized to the aldehyde via the reduction of the Cu(II)-radical active site. In the second half-reaction, O2 is reduced to H2O2, and the reduced Cu(I)-tyrosine site is oxidized to the initial Cu(II)-tyrosyl radical state. 

---