On the enzymatic activation of NADH

Atomic (1 Angstrom) resolution x-ray structures of horse liver alcohol dehy drogenase in complex with NADH revealed the formation of an adduct in the a ctive site between a metal-bound water and NADH. Furthermore, a pronounced distortion of the pyridine ring of NADH was observed, A series of quantum c hemical calculations on the water-nicotinamide adduct showed that the pucke ring of the pyridine ring in the crystal structures can only be reproduced when the water is considered a hydroxide ion, These observations provide fu ndamental insight into the enzymatic activation of NADH for hydride transfe r.