My laboratory is interested in how enzymes evolve and how they work. We are studying two groups of enzymes, the tautomerase superfamily and the fumaryl acetoacetate hydrolase (FAH) superfamily. Both superfamilies likely evolved from common ancestors through divergent evolution. The members of the tautomerase superfamily use a conserved amino-terminal proline and an arginine to catalyze diverse reactions including tautomerization, dehalogenation, hydration, and decarboxylation. The FAH superfamily members use an enzyme-bound metal ion to catalyze hydrolysis, decarboxylation, and perhaps hydration reactions.

Using a variety of mechanistic and structural techniques, we examine a range of reactions in these two groups so we can understand the principles used by Nature to make new enzymes from old ones. Understanding this process will enable us to design novel biocatalysts through rational design or directed evolution. This knowledge also has implications for the evolution of enzymes that degrade antibiotics (leading to antibiotic-resistant bacteria) and environmental pollutants.

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A) trans-3-chloroacrylic acid dehalogenase (CaaD), B) 4-oxalocrotonate tautomerase (4-OT), and C) malonate semialdehyde decarboxylase (MSAD) are structurally homologous enzymes that represent two families in the tautomerase superfamily. Sequence, structural, and mechanistic analysis suggest that these enzymes evolved from a common ancestor.

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Office: PHR 4.220C Phone: (512) 471-6198 Fax: (512) 232-2606 USMAIL: The University of Texas at Austin PHAR-MED CHEM PHR 4.220 1 University Station, A1935 Austin, TX 78712-0128

Lab: PHR 4.116, (512) 471-8860 FEDEX: The Division of Medicinal Chemistry College of Pharmacy, PHR 4.220 University of Texas at Austin Austin, TX 78712

Email: Whitman@mail.utexas.edu