Theoretical characterization of transition structure for the enzyme-catalyzed reaction at the active center of lactate dehydrogenase. Geometry and transition vector dependence upon computing method and model system

Abstract

A theoretical study of the catalytic mechanism of lactate dehydrogenase enzyme on different model systems was carried out with the help of the PM3 semi-empirical procedure and an ab initio method at the 4-31G and 6-31G** basis sets at a Hartree-Fock (HF) level of theory. The geometry, transition vector (TV) and electronic structure of the transition structure (TS) for the acid-catalysed hydride reduction were obtained. The dependence of these properties on the computing method and model system is analysed and discussed. Proton transfer is much more advanced than hydride transfer occurring in roughly perpendicular planes. All the TSs render very similar structural features, the control of the chemical reaction being associated with the hydride transfer process. A comparison among simple and sophisticated molecular models shows that the TS seems to be structurally a rather robust entity. There is a minimal molecular model with a TS which describes the essentials of the chemical interconversion step in a given enzyme mechanism and the corresponding TV is an invariant feature.