Download MendeleyInsight into a natural Diels-Alder reaction from the structure of macrophomate synthase.
Ose, T., Watanabe, K., Mie, T., Honma, M., Watanabe, H., Yao, M., Oikawa, H., Tanaka, I.(2003) Nature 422: 185-189
- PubMed: 12634789
- DOI: https://doi.org/10.1038/nature01454
- Primary Citation of Related Structures:
1IZC - PubMed Abstract:
The Diels-Alder reaction, which forms a six-membered ring from an alkene (dienophile) and a 1,3-diene, is synthetically very useful for construction of cyclic products with high regio- and stereoselectivity under mild conditions. It has been applied to the synthesis of complex pharmaceutical and biologically active compounds. Although evidence on natural Diels-Alderases has been accumulated in the biosynthesis of secondary metabolites, there has been no report on the structural details of the natural Diels-Alderases. The function and catalytic mechanism of the natural Diels-Alderase are of great interest owing to the diversity of molecular skeletons in natural Diels-Alder adducts. Here we present the 1.70 A resolution crystal structure of the natural Diels-Alderase, fungal macrophomate synthase (MPS), in complex with pyruvate. The active site of the enzyme is large and hydrophobic, contributing amino acid residues that can hydrogen-bond to the substrate 2-pyrone. These data provide information on the catalytic mechanism of MPS, and suggest that the reaction proceeds via a large-scale structural reorganization of the product.
Organizational Affiliation:
Division of Biological Science, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan.
