Theoretical computations (molecular dynamics and combined quantum chemical
and molecular mechanical geometry optimisations) have been performed on
horse liver alcohol dehydrogenase. The results provide evidence that Glu-68,
a highly conserved residue located 0.47 nm from the catalytic zinc ion,
may intermittently coordinate to the zinc ion. Structures with Glu-68 coordinated
to the zinc ion are almost as stable as structures
with Glu-68 at the crystal position and the barrier
between the two configurations of Glu-68 is so low
that it can readily be bypassed at room temperature. There is a cavity
behind the zinc ion that seems to be tailored to allow such coordination
of Glu-68 to the zinc ion. It is suggested that Glu-68 may facilitate
the exchange of ligands in the substrate site by coordinating to
the zinc ion when the old ligand dissociates.