The amino acid side chains whose variants satisfy the Brønsted relationship from Figure play the common role in catalysis of isomerization of stabilizing the enzyme-bound enediolate phosphate relative to bound substrate. The action of two types of side chains is modeled by this figure. First, the polar side chain cation of K12 favors substrate deprotonation by E165 through direct stabilization of negative charge at the enediolate oxygen of the reaction intermediate. EVB simulations (Table ) predict that the K12G substitution chain results in a 3.7 kcal mol -1 increase in ∆G ‡ for deprotonation of DHAP and a smaller 2.5 kcal mol -1 increase in ∆G ‡ for deprotonation of GAP, because the side chain lies closer to the O-2 compared to the O-1 oxyanions formed by deprotonation of DHAP and GAP, respectively (Figure ). The substitution results in larger 5.3 and 3.4 kcal mol -1 increases in ∆G 0 for deprotonation of enzymebound DHAP and GAP, respectively, because O-2 and O-1 now bear a full negative charge at the enediolate products.