Theoretical Study of Effects of Changing the Metal Inos on Glyoxalase II Reaction Mechanism

Metal ions are essential for the catalytic action of some enzymes. The most common role ofmetal ions is their ability to orient the substrate correctly for the reaction, exchange electrons inredox reactions, and stabilize negative charges. Glyoxalase II (GlxII) is a binuclear metalloenzymewith Zn(II) as the most frequently observed metal ion. However, cytosolic and mitochondrial GlxIIfrom Arabidopsis thaliana contains varying ratios of Zn(II), Fe(II), and Mn(II) [۱,۲]. Human GlxIIhas also been shown to contain a mixed binuclear center with Zn(II) and Fe(II), although themononuclear Zn(II) reconstituted enzyme is also active. This enzyme converts S-Dlactoylglutathioneto D-lactic acid. In this study, using quantum mechanics/molecular mechanics(QM/MM) calculations, the effect of changing the metal ions on the reaction mechanism of GlxIIwas investigated. A model of the active site of GlxII was constructed based on the crystal structureof the human GlxII (۱QH۵ PDB ID) [۳]. Besides, by changing the zinc ions of the active site withFe۲+ or Fe۳+ ions, we constructed other eight active site models. The reaction mechanism of GlxIIwas investigated by using these active site models and obtained energy profiles (cf. Figure ۱). Ourresults showed that the reaction mechanism of GlxII with two zinc ions in its active site has thelowest energy barrier which is in line with the higher preference of GlxII for zinc ion pairs in theactive site.

کلیدواژه ها:

Metalloprotein ، GlxII ، QM/MM ، DFT