Roll out the barrel scaffold

Work on (βα)₈-barrel proteins by a team at the European Molecular Biology Laboratory (EMBL, Hamburg, Germany) could provide insights into strategies for engineering new enzyme activities. In a study in Science (289, 1546–1550 , 2000), the EMBL team compared atomic structures of a group of related enzymes of the histidine biosynthesis pathway, HisA and HisF, and of the tryptophan biosynthesis pathway, TrpC, TrpF, and TrpA. Their analysis indicates that these enzymes evolved by gene duplication and diversification from an ancestral (βα)₈-barrel, itself the product of gene duplication and fusion of a (βα)₄-half barrel. Using random mutagenesis and selection, they also show that variants of HisA could be generated to catalyze the same reaction as TrpF, one of which retained its His A activity as well (PNAS 97 , 9925–9930, 2000). They suggest that a similar enzyme could have been an evolutionary precursor of both HisA and TrpF, although the possibility of TrpF evolving directly from HisA cannot be ruled out. The findings “should inspire other research into apparent single-domain proteins to discover they have also arisen by gene duplication,” speculates Stanford (CA) molecular biologist Charles Yanofsky. If successful, the work could be exploited to create new enzymes of industrial interest.