Modulating glyoxalase I metal selectivity by deletional mutagenesis: underlying structural factors contributing to nickel activation profiles.

Metabolically produced methylglyoxal is a cytotoxic compound that can lead to covalent modification of cellular DNA, RNA and protein. One pathway to detoxify this compound is via the glyoxalase enzyme system. The first enzyme of this detoxification system, glyoxalase I (GlxI), can be divided into two classes according to its metal activation profile, a Zn(2+)-activated class and a Ni(2+)-activated class.

Ni2+-activated glyoxalase I from Escherichia coli: substrate specificity, kinetic isotope effects and evolution within the βαβββ superfamily.

The Escherichia coli glyoxalase system consists of the metalloenzymes glyoxalase I and glyoxalase II. Little is known regarding Ni(2+)-activated E. coli glyoxalase I substrate specificity, its thiol cofactor preference, the presence or absence of any substrate kinetic isotope effects on the enzyme mechanism, or whether glyoxalase I might catalyze additional reactions similar to those exhibited by related βαβββ structural superfamily members.