title: Molecular mechanics calculation of geometries of NAD+ derivatives, modified in the nicotinamide group, in a ternary complex with horse liver alcohol dehydrogenase.
abstract: The geometry of seven NAD+ analogues bound to horse liver alcohol dehydrogenase (LADH) modified only in their nicotinamide group, have been studied using AMBER molecular mechanics energy-minimization procedures. Starting geometries were taken from X-ray crystallographic data for NAD+/Me2SO/LADH reported by Eklund and co-workers. In this study the NAD+ analogues were encaged by the constituent amino acids of the enzyme within a range of 0.6 nm from the initial NAD+/Me2SO/Zn2+ complex. The calculational method used is able to rationalize individual substituent effects and to evaluate the essential interactions between NAD+ analogue, enzyme, Me2SO and Zn2+ without the necessity of additional X-ray data. The results presented here demonstrate that the reactivity of NAD+ derivatives as reported in literature can be qualitatively related to the position of the pyridine moiety in the active site.
authors.affiliation: Department of Organic Chemistry, Eindhoven University of Technology, The Netherlands.
authors.forename: P M
authors.initials: PM
authors.lastname: de Kok
authors.forename: N A
authors.initials: NA
authors.lastname: Beijer
authors.forename: H M
authors.initials: HM
authors.lastname: Buck
authors.forename: L A
authors.initials: LA
authors.lastname: Sluyterman
authors.forename: E M
authors.initials: EM
authors.lastname: Meijer
mesh_terms: D000426:Alcohol Dehydrogenase / Q000032:analysis*; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001665:Binding Sites; D055598:Chemical Phenomena; D002621:Chemistry; D004735:Energy Transfer; D006736:Horses; D008099:Liver / Q000201:enzymology; D008968:Molecular Conformation; D009243:NAD / Q000031:analogs & derivatives / Q000032:analysis*; D009536:Niacinamide / Q000032:analysis*; D011485:Protein Binding
chemical_list: D000596:Amino Acids; D009243:NAD; D009536:Niacinamide; D000426:Alcohol Dehydrogenase