STRUCTURAL AND SEQUENCE COMPARISONS OF QUINONE OXIDOREDUCTASE, ZETA-CRYSTALLIN, AND GLUCOSE AND ALCOHOL DEHYDROGENASES

Quinone oxidoreductase, xi-crystallin, glucose dehydrogenase, and alco hol dehydrogenase belong to a superfamily of medium-chain dehydrogenas e/reductases, The crystal structures of Escherichia coli quinone oxido reductase (QOR) and Thermoplasma acidophilun glucose dehydrogenase hav e recently been determined and are compared here with the well-known s tructure of horse liver alcohol dehydrogenase. A structurally based co mparison of these three enzymes confirms that they possess extensive o verall structural homology despite low sequence identity, The most sig nificant difference is the absence of the catalytic and structural zin c ions in QOR, A multiple structure-based sequence alignment has been constructed for the three enzymes and extended to include xi-crystalli n, an eye lens structural protein with quinone oxidereductase activity and high sequence identity to E. coli quinone oxidoreductase. Residue s which are important for catalysis have been altered and the function s and activities of the enzymes have diverged, illustrating a classic example of divergent evolution among a superfamily of enzymes, (C) 199 6 Academic Press, Inc.