Enzymes are macromolecules, which play a vital role in catalyzing chemical reactions inside living cells. The metalloenzyme glyoxalase I converts the nonenzymatically produced hemimercaptal of cytotoxic methylglyoxal and glutathione to nontoxic S-Dlactoylglutathione. Escherichia coli enzyme is inactive in presence of Zn2+ and is maximally active with Ni2+. we used DFT approaches to increase the understanding of the mechanistic aspect of glyoxalase I from Escherichia coli. In this work, we use the crystal approach to model GlxI and study its catalytic mechanism. The results showed that the reaction path is independent of the model size and the fixed atom pattern. Nevertheless, the energy profile is dependent to size and flexibility of the models.
