"Lethal Synthesis" of Fluorocitrate by Citrate Synthase Explained through QM/MM Modeling

A classic example of enzyme stereospecificity is the title reaction involving the enantioselective conversion of fluoroacetyl‐CoA. High‐level modeling of the enzyme reaction shows that preferential formation of an E‐enolate explains the experimentally observed specificity. The results indicate that selectivity is primarily a result of the inherent energy difference between the E‐ and Z‐enolates of fluoroacetyl‐CoA.