SEMINAR: Bayliss Seminar Series

of enzyme allostery may not apply to DHDPS. However, we show using biophysical analyses that DHDPS from Triticum aestivum (i.e. bread wheat) is allosterically regulated by lysine-induced dissociation of the active oligomeric species. This represents a rare example of the morpheein allosteric model – also known as the dissociative concerted mechanism – first proposed by Jaffe in 2005. Interestingly, our studies suggest that DHDPS is regulated by morpheein principles, but that the mechanism is different in bacterial and plant species. Moreover, the allosteric model appears to be a dissociative concerted process for T. aestivum DHDPS, where the binding of lysine induces dissociation of active tetramers to inactive dimers. By contrast, the binding of lysine to DHDPS from the bacterium Vibrio cholerae appears to conform to an associative concerted mechanism, where lysine induces association of the active dimeric form to an inactive tetrameric state. This is the first case where opposing morpheein principles have been observed for orthologues from bacteria and plants. Accordingly, this mechanism has been coined the Ligand-Induced dis/associatioN by Lysine (K) (LINK) model, which offers insight into the evolution of enzyme allostery and quaternary structure.