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Evolution of Protein Structure and Function
How do protein sequence and structure mediate protein function? Evolution is the organizing principle of biology and provides the cornerstone of our approach to answering this deceptively simple question. We use large scale bioinformatic analysis to place biochemical data into evolutionary and biological context, and we experimentally test hypotheses derived from these bioinformatic studies to analyze protein structure-function relationships. Our primary focus is determining how structure and function coevolve to preserve function or to evolve new activities. We are applying this knowledge to predicting protein functions, correcting misannotations from genome sequencing projects, and improving protein engineering strategies.The subject of our current research is the mechanistically diverse enolase superfamily. Enzymes in this superfamily are evolutionarily related and share a set of conserved catalytic residues that perform a common partial reaction (abstracting a proton adjacent to a carboxylate and stabilizing the resulting enolate anion intermediate). Using these conserved residues and additional active site residues, different families in the enolase superfamily not only bind different substrates, but also catalyze diverse overall reactions, including racemization of modified amino acids and dehydration of several different acid sugars. There are over 1000 proteins in the superfamily, and over fifteen different isofunctional families have been identified. About half of the proteins in the superfamily have unknown functions. Our areas of research include:
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Recent Publications |