Eliminating Competition: Characterizing and Eliminating Competitive Binding at Separate Sites between DAHP Synthase’s Essential Metal Ion and the Inhibitor DAHP Oxime

3-Deoxy-d- arabinoheptulosonate 7-phosphate (DAHP) oxime is a transition state mimic inhibitor of bacterial DAHP synthase, with K _i = 1.5 μM and a residence time of t_R = 83 min. Unexpectedly, DAHP oxime inhibition is competitive with respect to the essential metal ion, Mn²⁺, even though the inhibitor and metal ion do not occupy the same physical space in the active site. This is problematic because DAHP synthase is activated by multiple …