Density functional theory has been used to study the mechanism and stereospecificity of the
catalytic reaction of human glyoxalase I. We used the quantum mechanical cluster method to
model the enzyme active site. Glyoxalase I accepts both enantiomers of the hemithioacetal
between methylglyoxal and glutathione and converts them to the SD enantiomer of
lactoylglutathione. We have compared several previously suggested or alternative reaction
mechanisms for both substrates on an equal footing. The results show that the coordination …