The coordination chemistry of the structural zinc ion in alcohol dehydrogenase studied by ab initio quantum chemical calculation

Ulf Ryde
Eur. J. Biophys.  24 (1996)213-221

The coordination chemistry of the structural zinc ion in horse liver alcohol dehydrogenase has been examined by quantum chemical geometry optimisations. It is shown that all the four cysteine ligands are deprotonated in the enzyme, not only two of them as has been suggested. The Zn-S bond lengths are very sensitive to the theoretical treatment; in vacuum they are predicted to be 15 pm longer than in the crystal structure. Half of this discrepancy is due to electronic correlation, the rest can be attributed to screening of the negative sulphide charges by the enzyme, in particular by NH-S hydrogen bonds. The potential surface is rather flat, so the large difference in geometry between the crystal and the vacuum structure corresponds to an energy change of less than 35 kJ/mole. The crystal bond lengths can be reproduced only with methods that accounts explicitly for the enzyme. A dielectric continuum model gives too long bond lengths, indicating that the enzyme solvates the coordination sphere better than water. Thus, the structural zinc ion can be used as a sensitive test of methods trying to model the surrounding medium in quantum chemical computations.