title: On the molecular mechanism of liver alcohol dehydrogenase: Monte Carlo simulations and X-ray studies of water in the substrate channel.
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.
mesh_terms: D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008958:Models, Molecular; D009010:Monte Carlo Method; D011487:Protein Conformation; D014867:Water / Q000032:analysis; D014961:X-Ray Diffraction
chemical_list: D014867:Water; D000426:Alcohol Dehydrogenase