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Project Progress

Analysis of molecular events in the period before the Last Common Ancestor has continued. Earlier work emphasized the molecular events involved in divergence from a common ancestral protein to generate progeny proteins of diverse function. Current work is focused on related groups of enzymes, with the goal of identifying ancestral types of proteins capable of generating many types of progeny enzymes.

We have studied in detail two types of protein families in E. coli and other bacteria. One type is close-knit with all relatives in contemporary organisms well-related both in conserved regions of the protein sequence and in function. Our chosen example is a group of aminotransferases. Sequences of Class III transaminases have three major regions of conservation. One binds the cofactor, pyridoxal phosphate, another binds an amino acid donor, and a third is the core region. Given the demonstrably close relationships of sequence and structure of transaminases, it is easy to suppose they share a common transaminase ancestor and that they differ today not in chemistry of reaction but only in what substrate is bound, that is, substrate specificity.

The other type of related enzymes we have studied is more complex and thus more interesting from an evolutionary point of view. Some protein families differ not only in specificity of small molecule bound but also in the actual reaction catalyzed. We have studied closely two such families: the crotonase family and the thiamine diphosphate dependent decarboxylase family of E. coli and other bacteria. Each may represent a single early ancestral protein, and each gave rise to a family of enzymes that carry out many kinds of reactions having only basic chemistry in common.