On the Molecular Mechanism of Liver Alcohol Dehydrogenase: Monte Carlo Simulations and X-Ray Studies of Water in the Substrate Channel

Publisher Website
Google Scholar
Abstract
Water structure in the substrate channel of liver alcohol dehydrogenase as a function of the oxidation state of the coenzyme nicotinamide ring has been studied with Monte Carlo simulations. X-ray data on water structure has been analyzed. The simulations show an order-disorder effect in the water distribution produced by the charge state of the ring; also, solvation-desolvation effects are detected. For positively charged ring, the water molecules form a fluctuated H-bonded network that connects the deeply buried active site zinc to the bulk solvent. This network together with the side chain of Ser-48 most likely is the support for a proton relay system thereby providing a mechanism responsible of the pKa shift of the zinc-bound water as it is produced by the oxidized coenzyme binding.