ON THE ROLE OF GLU-68 IN ALCOHOL-DEHYDROGENASE

Theoretical computations (molecular dynamics and combined quantum chem ical and molecular mechanical geometry optimizations) have been perfor med on horse liver alcohol dehydrogenase. The results provide evidence that Glu-68, a highly conserved residue located 0.47 nm from the cata lytic zinc ion, may intermittently coordinate to the zinc ion. Structu res with Glu-68 coordinated to the zinc ion are almost as stable as st ructures with Glu-68 at the crystal position and the barrier between t he two configurations of Glu-68 is so low that it can readily be bypas sed at room temperature. There is a cavity behind the zinc ion that se ems to be tailored to allow such coordination of Glu-68 to the zinc io n. 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 lig and dissociates.