9VSM

Crystal structure of cystathionine gamma-synthase from Lactobacillus plantarum complexed with the cystathionine-bound external aldimine

Summary for 9VSM

• Entry DOI: 10.2210/pdb9vsm/pdb
• Descriptor: Cysteine gamma synthase/O-succinylhomoserine (Thiol)-lyase, (2~{S})-4-[(2~{R})-2-azanyl-3-oxidanyl-3-oxidanylidene-propyl]sulfanyl-2-[(~{E})-[2-methyl-3-oxidanyl-5-(phosphonooxymethyl)pyridin-4-yl]methylideneamino]butanoic acid (3 entities in total)
• Functional Keywords: cystathionine gamma-synthase, transferase
• Biological source: Lactiplantibacillus plantarum (strain ATCC BAA-793 / NCIMB 8826 / WCFS1)
• Total number of polymer chains: 4
• Total formula weight: 168072.38

Authors

Oda, K.,Matoba, Y. (deposition date: 2025-07-09, release date: 2026-02-04)

Primary citation

Matoba, Y.,Oda, K.,Ohtani, M.,Mende, Y.,Noda, K.
Structural insight into the substrate specificity of cystathionine gamma-synthase from Lactobacillus plantarum.
Febs Lett., 2026

PubMed Abstract: 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 LpCGS and LpCGL may provide insights into their reaction specificities. In the present study, we elucidated the structure and enzymatic function of LpCGS. We found that LpCGS has substrate specificity toward acetylated rather than succinylated l-homoserine. LpCGS 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.

PubMed: 41562399
DOI: 10.1002/1873-3468.70276

Experimental method

X-RAY DIFFRACTION (1.58 Å)