7PXO
Structure of the Diels Alderase enzyme AbyU, from Micromonospora maris, co-crystallised with a non transformable substrate analogue
Summary for 7PXO
| Entry DOI | 10.2210/pdb7pxo/pdb |
| Descriptor | YD repeat-containing protein, (Z,2R,4S)-1-(4-methoxy-5-methylidene-2-oxidanylidene-furan-3-yl)-2,4-dimethyl-dodec-6-ene-1,5-dione, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (4 entities in total) |
| Functional Keywords | diels alderase, complex, abyssomicin, substrate, ligase |
| Biological source | Micromonospora maris AB-18-032 |
| Total number of polymer chains | 4 |
| Total formula weight | 72815.81 |
| Authors | Back, C.R.,Race, P.R. (deposition date: 2021-10-08, release date: 2022-11-16, Last modification date: 2024-12-25) |
| Primary citation | Maschio, L.,Back, C.R.,Alnawah, J.,Bowen, J.I.,Johns, S.T.,Mbatha, S.Z.,Han, L.C.,Lees, N.R.,Zorn, K.,Stach, J.E.M.,Hayes, M.A.,van der Kamp, M.W.,Pudney, C.R.,Burston, S.G.,Willis, C.L.,Race, P.R. Delineation of the complete reaction cycle of a natural Diels-Alderase. Chem Sci, 15:11572-11583, 2024 Cited by PubMed Abstract: The Diels-Alder reaction is one of the most effective methods for the synthesis of substituted cyclohexenes. The development of protein catalysts for this reaction remains a major priority, affording new sustainable routes to high value target molecules. Whilst a small number of natural enzymes have been shown capable of catalysing [4 + 2] cycloadditions, there is a need for significant mechanistic understanding of how these prospective Diels-Alderases promote catalysis to underpin their development as biocatalysts for use in synthesis. Here we present a molecular description of the complete reaction cycle of the natural Diels-Alderase AbyU, which catalyses formation of the spirotetronate skeleton of the antibiotic abyssomicin C. This description is derived from X-ray crystallographic studies of AbyU in complex with a non-transformable synthetic substrate analogue, together with transient kinetic analyses of the AbyU catalysed reaction and computational reaction simulations. These studies reveal the mechanistic intricacies of this enzyme system and establish a foundation for the informed reengineering of AbyU and related biocatalysts. PubMed: 39055018DOI: 10.1039/d4sc02908a PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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