title: On the enzymatic activation of NADH.
abstract: Atomic (1 A) resolution x-ray structures of horse liver alcohol dehydrogenase in complex with NADH revealed the formation of an adduct in the active site between a metal-bound water and NADH. Furthermore, a pronounced distortion of the pyridine ring of NADH was observed. A series of quantum chemical calculations on the water-nicotinamide adduct showed that the puckering of the pyridine ring in the crystal structures can only be reproduced when the water is considered a hydroxide ion. These observations provide fundamental insight into the enzymatic activation of NADH for hydride transfer.
authors.affiliation: European Molecular Biology Laboratory, c/o DESY, Notkestrasse 85, 22603 Hamburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Meijers
authors.forename: R J
authors.initials: RJ
authors.lastname: Morris
authors.forename: H W
authors.initials: HW
authors.lastname: Adolph
authors.forename: A
authors.initials: A
authors.lastname: Merli
authors.forename: V S
authors.initials: VS
authors.lastname: Lamzin
authors.forename: E S
authors.initials: ES
authors.lastname: Cedergren-Zeppezauer
mesh_terms: D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004577:Electron Probe Microanalysis; D006736:Horses; D008099:Liver / Q000201:enzymology; D008958:Models, Molecular; D009243:NAD / Q000737:chemistry / Q000378:metabolism*
chemical_list: D009243:NAD; D000426:Alcohol Dehydrogenase