Mehdi Irani
University of Kurdistan, Iran
Title: On the special specificity of Glyoxalase I, a Metalloenzyme that accepts both enantiomers of its chiral substrate but converts them to only the S-D enantiomer of lactoylglutathione
Biography
Biography: Mehdi Irani
Abstract
Glyoxalase I (GlxI) is a member of the glyoxalase system, which is important in cell detoxification and converts hemithioacetals of methylglyoxal (a cytotoxic byproduct of sugar metabolism) and glutathione into D-lactate. GlxI accepts both S and R enantiomers of hemithioacetal, but converts them to only the S-D enantiomer of lactoylglutathione. Interestingly, the enzyme shows this unusual specificity with a rather symmetric active site (a Zn ion coordinated to two glutamate residues; Glu-99 and Glu-172). Recently, we have studied different aspects of the GlxI reaction in four separate works using computational chemistry methods [1–4]. Our Molecular dynamics simulations and hybrid quantum mechanics/molecular mechanics calculations show that Glu-172 is more flexible and basic than Glu-99 in the catalytic reaction of GlxI and is much closer to flexible loops inside the protein. In addition, the higher basicity and flexibility of Glu-172 may explain the special stereospecificity of GlxI.