Methionine is one of the sulfur-containing amino acids found in proteins which is considered the most hydrophobic specie among the amino acids. Methionine is responsible for the protein synthesis, methylation of DNA and polyamine synthesis in human body. Deprivations of methionine can be used to reduce methionine both in plasma and tumor. Many investigators have attempted to exploit the methionine dependence of tumors for therapeutic effects in vivo. Since methionine free-diet is inefficient due to practical considerations, enzymatic degradation of methionine can be used as an alternative treatment method for cancer. In this study, the enzymatic degradation mechanism of L-methionine was computationally investigated into three sections: internal aldimine formation, external aldimine formation and methionine degradation, respectively.
Density functional theory (DFT) study was carried to elucidate enzymatic reaction mechanism of methionine – reactants, transition states, intermediates and products optimized in gas phase. Additionally, frequency analyses were performed and the intrinsic reaction coordinate (IRC) scans were conducted to ensure TSs lead to the corresponding reactants and products.