New Nature Chemical Biology paper


Nature Chemical Biology Abstract Binding protein to enzyme Jackson Clifton


It’s out! Our Nature Chemical Biology paper “Evolution of cyclohexadienyl dehydratase from an ancestral solute-binding protein” is now online. 

How do new enzymes evolve from proteins that were initially specialised for binding? In this work, we use ancestral protein reconstruction to calculate and characterise the evolutionary intermediate states linking an ancestral solute-binding protein to the extant enzyme cyclohexadienyl dehydratase. We show how the intrinsic reactivity of a desolvated general acid was harnessed by a series of mutations radiating from the active site, which optimized enzyme–substrate complementarity and transition-state stabilization and minimized sampling of noncatalytic conformations.

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