9UEJ

Cryo-EM structure of L-lysine 6-dehydrogenase

Summary for 9UEJ

• Entry DOI: 10.2210/pdb9uej/pdb
• EMDB information: 64083
• Descriptor: Lysine 6-dehydrogenase (1 entity in total)
• Functional Keywords: dehydrogenase, apo, amino acid, enzyme, oxidoreductase
• Biological source: Geobacillus stearothermophilus
• Total number of polymer chains: 4
• Total formula weight: 168841.80

Authors

Funahashi, T.,Yamaguchi, H.,Suzuki, S.,Suzuki, H.,Nishikawa, K.,Kazutoshi, T.,Fujiyoshi, Y.,Sugiki, M. (deposition date: 2025-04-08, release date: 2026-09-16)

Primary citation

Funahashi, T.,Yamaguchi, H.,Suzuki, S.,Suzuki, H.,Nishikawa, K.,Takahashi, K.,Tatsumi, M.,Mizukoshi, T.,Miyano, H.,Fujiyoshi, Y.,Sugiki, M.
Structural basis for substrate recognition in l-lysine 6-dehydrogenase from Geobacillus stearothermophilus by Cryo-EM.
J.Struct.Biol., 218:108366-108366, 2026

PubMed Abstract: l-lysine 6-dehydrogenase (LysDH; EC 1.4.1.18) oxidatively deaminates the ε-amino group of l-lysine. Due to its high substrate specificity, LysDH serves as a valuable tool for l-lysine quantification. However, the molecular basis of this specificity has remained unclear because of the lack of substrate-bound structures. In this study, we determined the cryo-electron microscopy (cryo-EM) structures of LysDH from the thermophilic bacterium Geobacillus stearothermophilus (GstLysDH) in the apo form at 2.9 Å resolution and in complex with NAD and l-lysine at 2.5 Å resolution. GstLysDH assembles as a tetramer, which undergoes a global conformational transition upon NAD binding. Structural analysis revealed that the α-carboxyl and α-amino groups of l-lysine were coordinated by oppositely charged residues, thereby orienting the ε-amino group toward the nicotinamide ring of NAD and anchoring the substrate in the optimal binding mode. This precise recognition mechanism accounts for the enzyme's strict specificity for the ε-amino group of l-lysine. Furthermore, comparative structural analysis with l-phenylalanine dehydrogenase suggests that the oxidative deamination in GstLysDH proceeds through a conserved hydride transfer mechanism. Together, these insights establish a structural framework for the rational design and industrial application of LysDH and related amino acid dehydrogenases.

PubMed: 42665198
DOI: 10.1016/j.jsb.2026.108366

Experimental method

ELECTRON MICROSCOPY (2.94 Å)