8RYE
AzeJ in complex with MTA and AZE from Pseudomonas aeruginosa (P2(1)2(1)2)
Summary for 8RYE
| Entry DOI | 10.2210/pdb8rye/pdb |
| Descriptor | Class I SAM-dependent methyltransferase, 5'-DEOXY-5'-METHYLTHIOADENOSINE, (2S)-azetidine-2-carboxylic acid, ... (6 entities in total) |
| Functional Keywords | natural product biosynthesis, non-proteinogenic amino acid, proline-homologue, sam-turnover, catalysis, lyase |
| Biological source | Pseudomonas aeruginosa |
| Total number of polymer chains | 4 |
| Total formula weight | 112839.09 |
| Authors | Klaubert, T.J.,Gellner, J.,Bernard, C.,Effert, J.,Lombard, C.,Kaila, V.R.I.,Bode, H.B.,Li, Y.,Groll, M. (deposition date: 2024-02-08, release date: 2025-01-01, Last modification date: 2025-02-19) |
| Primary citation | 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 Cited by 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: 39905070DOI: 10.1038/s41467-025-56610-6 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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