Structural insight into the substrate specificity of cystathionine γ‐synthase from Lactobacillus plantarum

Cystathionine γ‐synthase (CGS) and cystathionine γ‐lyase (CGL) have highly similar amino acid sequences. CGS catalyzes the generation of cystathionine from acylated l ‐homoserine and l ‐cysteine, whereas CGL catalyzes the decomposition of cystathionine to produce l ‐cysteine. Lactobacillus plantarum is a unique bacterium containing two open reading frames of CGL/CGS enzymes in its genome. Structural studies of Lp CGS and Lp CGL may provide insights into their reaction specificities. In the present study, we elucidated the structure and enzymatic function of Lp CGS. We found that Lp CGS has substrate specificity toward acetylated rather than succinylated l ‐homoserine. Lp CGS has the characteristic residues E55 and V232 in the substrate‐binding pocket, which synergistically confer substrate specificity toward acetylated l ‐homoserine. These results may facilitate the development of inhibitors of l ‐methionine and l ‐cysteine biosynthetic pathways.