Divergent evolution of (beta alpha)(8)-barrel enzymes

The (beta alpha)(8)-barrel is the most versatile and most frequently encoun tered fold among enzymes. It is an interesting question how the contemporar y (beta alpha)(8)-barrels are evolutionarily related and by which mechanism s they evolved from more simple precursors. Comprehensive comparisons of am ino acid sequences and three-dimensional structures suggest that a large fr action of the known (beta alpha)(8)-barrels have divergently evolved from a common ancestor. The mutational interconversion of enzymatic activities of several (beta alpha)(8)-barrels further supports their common evolutionary origin. Moreover, the high structural similarity between the N- and C-term inal (beta alpha)(4) units of two (beta alpha)(8)-barrel enzymes from histi dine biosynthesis indicates that the contemporary proteins evolved by tande m duplication and fusion of the gene of an ancestral 'half-barrel' precurso r. In support of this hypothesis, recombinantly produced 'half-barrels' wer e shown to be folded, dimeric proteins.