8RYE

AzeJ in complex with MTA and AZE from Pseudomonas aeruginosa (P2(1)2(1)2)

8RYE の概要

• エントリーDOI: 10.2210/pdb8rye/pdb
• 分子名称: Class I SAM-dependent methyltransferase, 5'-DEOXY-5'-METHYLTHIOADENOSINE, (2S)-azetidine-2-carboxylic acid, ... (6 entities in total)
• 機能のキーワード: natural product biosynthesis, non-proteinogenic amino acid, proline-homologue, sam-turnover, catalysis, lyase
• 由来する生物種: Pseudomonas aeruginosa
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 112839.09

構造登録者

Klaubert, T.J.,Gellner, J.,Bernard, C.,Effert, J.,Lombard, C.,Kaila, V.R.I.,Bode, H.B.,Li, Y.,Groll, M. (登録日: 2024-02-08, 公開日: 2025-01-01, 最終更新日: 2025-02-19)

主引用文献

Klaubert, T.J.,Gellner, J.,Bernard, C.,Effert, J.,Lombard, C.,Kaila, V.R.I.,Bode, H.B.,Li, Y.,Groll, M.
Molecular basis for azetidine-2-carboxylic acid biosynthesis.
Nat Commun, 16:1348-1348, 2025

PubMed Abstract: Azetidine-2-carboxylic acid (AZE) is a long-known plant metabolite. Recently, AZE synthases have been identified in bacterial natural product pathways involving non-ribosomal peptide synthetases. AZE synthases catalyse the intramolecular 4-exo-tet cyclisation of S-adenosylmethionine (SAM), yielding a highly strained heterocycle. Here, we combine structural and biochemical analyses with quantum mechanical calculations and mutagenesis studies to reveal catalytic insights into AZE synthases. The cyclisation of SAM is facilitated by an exceptional substrate conformation and supported by desolvation effects as well as cation-π interactions. In addition, we uncover related SAM lyases in diverse bacterial phyla, suggesting a wider prevalence of AZE-containing metabolites than previously expected. To explore the potential of AZE as a proline mimic in combinatorial biosynthesis, we introduce an AZE synthase into the pyrrolizixenamide pathway and thereby engineer analogues of azabicyclenes. Taken together, our findings provide a molecular framework to understand and exploit SAM-dependent cyclisation reactions.

PubMed: 39905070
DOI: 10.1038/s41467-025-56610-6

実験手法

X-RAY DIFFRACTION (1.95 Å)