7C3J

Structure of L-lysine oxidase D212A/D315A in complex with L-phenylalanine

7C3J の概要

• エントリーDOI: 10.2210/pdb7c3j/pdb
• 関連するPDBエントリー: 3X0V 7C3H 7C3I
• 分子名称: L-lysine oxidase, FLAVIN-ADENINE DINUCLEOTIDE, PHENYLALANINE, ... (6 entities in total)
• 機能のキーワード: l-amino acid oxidase, oxidoreductase
• 由来する生物種: Hypocrea rufa
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 124037.18

構造登録者

Kitagawa, M.,Matsumoto, Y.,Inagaki, K.,Imada, K. (登録日: 2020-05-12, 公開日: 2020-09-23, 最終更新日: 2023-11-29)

主引用文献

Kondo, H.,Kitagawa, M.,Matsumoto, Y.,Saito, M.,Amano, M.,Sugiyama, S.,Tamura, T.,Kusakabe, H.,Inagaki, K.,Imada, K.
Structural basis of strict substrate recognition of l-lysine alpha-oxidase from Trichoderma viride.
Protein Sci., 29:2213-2225, 2020

PubMed Abstract: l-Lysine oxidase (LysOX) is a FAD-dependent homodimeric enzyme that catalyzes the oxidative deamination of l-lysine to produce α-keto-ε-aminocaproate with ammonia and hydrogen peroxide. LysOX shows strict substrate specificity for l-lysine, whereas most l-amino acid oxidases (LAAOs) exhibit broad substrate specificity for l-amino acids. Previous studies of LysOX showed that overall structural similarity to the well-studied snake venom LAAOs. However, the molecular mechanism of strict specificity for l-lysine was still unclear. We here determined the structure of LysOX in complex with l-lysine at 1.7 Å resolution. The structure revealed that the hydrogen bonding network formed by D212, D315, and A440 with two water molecules is responsible for the recognition of the side chain amino group. In addition, a narrow hole formed by five hydrophobic residues in the active site contributes to strict substrate specificity. Mutation studies demonstrated that D212 and D315 are essential for l-lysine recognition, and the D212A/D315A double mutant LysOX showed different substrate specificity from LysOX. Moreover, the structural basis of the substrate specificity change has also been revealed by the structural analysis of the mutant variant and its substrate complexes. These results clearly explain the molecular mechanism of the strict specificity of LysOX and suggest that LysOX is a potential candidate for a template to design LAAOs specific to other l-amino acids.

PubMed: 32894626
DOI: 10.1002/pro.3946

実験手法

X-RAY DIFFRACTION (2.2 Å)