title: The chemical versatility of the beta-alpha-beta fold: catalytic promiscuity and divergent evolution in the tautomerase superfamily.
abstract: Tautomerase superfamily members have an amino-terminal proline and a beta-alpha-beta fold, and include 4-oxalocrotonate tautomerase (4-OT), 5-(carboxymethyl)-2-hydroxymuconate isomerase (CHMI), trans- and cis-3-chloroacrylic acid dehalogenase (CaaD and cis-CaaD, respectively), malonate semialdehyde decarboxylase (MSAD), and macrophage migration inhibitory factor (MIF), which exhibits a phenylpyruvate tautomerase (PPT) activity. Pro-1 is a base (4-OT, CHMI, the PPT activity of MIF) or an acid (CaaD, cis-CaaD, MSAD). Components of the catalytic machinery have been identified and mechanistic hypotheses formulated. Characterization of new homologues shows that these mechanisms are incomplete. 4-OT, CaaD, cis-CaaD, and MSAD also have promiscuous activities with a hydratase activity in CaaD, cis-CaaD, and MSAD, PPT activity in CaaD and cis-CaaD, and CaaD and cis-CaaD activities in 4-OT. The shared promiscuous activities provide evidence for divergent evolution from a common ancestor, give hints about mechanistic relationships, and implicate catalytic promiscuity in the emergence of new enzymes.
authors.affiliation: Department of Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, Netherlands.
authors.forename: G J
authors.initials: GJ
authors.lastname: Poelarends
authors.forename: V Puthan
authors.initials: VP
authors.lastname: Veetil
authors.forename: C P
authors.initials: CP
authors.lastname: Whitman
mesh_terms: D019748:Carbon-Carbon Double Bond Isomerases / Q000737:chemistry / Q000235:genetics*; D002262:Carboxy-Lyases / Q000737:chemistry / Q000235:genetics*; D002384:Catalysis; D019143:Evolution, Molecular; D006867:Hydrolases / Q000737:chemistry / Q000235:genetics*; D007535:Isomerases / Q000737:chemistry / Q000235:genetics*; D008263:Macrophage Migration-Inhibitory Factors / Q000737:chemistry / Q000235:genetics*; D008958:Models, Molecular; D017433:Protein Structure, Secondary / Q000235:genetics*
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D006867:Hydrolases; C077719:cis-3-chloroacrylic acid dehalogenase; C077721:trans-3-chloroacrylic acid dehalogenase; D002262:Carboxy-Lyases; C071850:malonate semialdehyde decarboxylase; C021918:4-oxalocrotonate tautomerase; D007535:Isomerases; D019748:Carbon-Carbon Double Bond Isomerases; C031939:5-carboxymethyl-2-hydroxymuconate delta-isomerase