Enzyme promiscuity : a review on select tautomerase superfamily members

Enzymes are categorized into families based on sequence similarity and conserved features. Superfamilies are composed of families of enzymes with common folds and conserved features. Enzymes with broad specificities are able to evolve into different enzymes with new chemistries. However, they still contain vestigial folds and conserved residues that traces their evolution back to that broad specificity ancestor. Three enzymes from the Tautomerase Superfamily will be discussed here, all related by a N-terminal catalytic proline and the use of the β-α-β building block. The structures, mechanisms, and promiscuous activities of 4-oxalocrotonate tautomerase, 3-chloroacrylic dehalogenase, and malonate semialdehyde decarboxylase are discussed. All three are evolutionarily linked through a shared promiscuous hydration activity using 2-oxo-3-pentyoate and likely came from the same ancestor.Pharmac