Molecular Mechanism of Stereospecificity toward D-Leucine of the Transaminase from Desulfohalobium retbaense Revealed by Molecular Dynamic Simulations

The results of a molecular dynamics study of the molecular mechanism of the experimentally observed specificity of the transaminase from Desulfohalobium retbaense (Dret) to the D-isomer of leucine are presented. A full-atom 3D model of Dret is constructed based on the data on the primary sequence and the information on the crystal structures of the related enzymes. The analysis of the trajectories of the molecular dynamics demonstrates that, upon the formation of the enzyme-substrate complex with D-leucine, the α-COO– group of the substrate forms stable hydrogen bonds with the Arg54* residue, which promotes the proper orientation of the substrate in the active site. The formation of the complex with the L-isomer of leucine leads to disraption of these hydrogen bonds and of the structure of the active site.