Abstract
The crystal structure of natural Diels-Alderase, macrophomate synthase, in complex with pyruvate was determined at 1.7 Å resolution. The structure explains broad substrate specificity and provides mechanistic information regarding the multiple catalyst of this enzyme. The active site reveals several ingenious features for catalyzing the Diels-Alder reaction, which include the existence of residues for making catalytically important hydrogen bonds to the 2-pyrone. The rather large and hydrophobic milieu in the active site cavity allows a large-scale structural reorganization of the product imposed to escape product inhibition. These findings are useful for understanding the strategy of a natural Diels-Alderase, which have been acquired during a long time evolution.
