On the enzymatic activation of NADH.
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.
Meijers
R
R
European Molecular Biology Laboratory, c/o DESY, Notkestrasse 85, 22603 Hamburg, Germany.
Morris
R J
RJ
Adolph
H W
HW
Merli
A
A
Lamzin
V S
VS
Cedergren-Zeppezauer
E S
ES
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*
D009243:NAD; D000426:Alcohol Dehydrogenase