7PXO

Structure of the Diels Alderase enzyme AbyU, from Micromonospora maris, co-crystallised with a non transformable substrate analogue

7PXO の概要

• エントリーDOI: 10.2210/pdb7pxo/pdb
• 分子名称: 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)
• 機能のキーワード: diels alderase, complex, abyssomicin, substrate, ligase
• 由来する生物種: Micromonospora maris AB-18-032
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 72815.81

構造登録者

Back, C.R.,Race, P.R. (登録日: 2021-10-08, 公開日: 2022-11-16, 最終更新日: 2024-12-25)

主引用文献

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

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: 39055018
DOI: 10.1039/d4sc02908a

実験手法

X-RAY DIFFRACTION (1.95 Å)