Abstract
We present quantum chemical calculations, through 6-311G**/B3LYP, for the isomerization step in D-Xylose Isomerase, based on truncated models of the 3KCO (linear) and 3KCL (cyclic) X-ray/neutron structures, containing 9 free waters, 2 metals, the sugar and roughly 19 amino acids. Perturbative relaxations upon the experimental framework suggest a possible seven-step mechanism of the isomerzation reaction involving direct ionization of the glucose O2 proton on movement of the mobile magnesium ion (Mg2A → 2B). In this model, we also find a compensating proton shift between the K183/D255 pair, corresponding to a 10kcal/mol reduction in the cost of the ionization, with a delocalized shift in potential along the reaction plane. We find ~16 kcal/mol reaction barriers in reasonable agreement with experiment (14 kcal/mol), as well as a final, exothermic hydroxide consistent with the 3CWH (product) structure, and possibly explaining observed non-Michaelis behavior of this enzyme.