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.