The crystal structure of complexes between horse liver alcohol dehydrogenase and the coenzyme analogues 3-iodopyridine-adenine dinucleotide and pyridine-adenine dinucleotide.
We have studied the binding of the enzymatically active NAD+ analogue, 3-iodopyridine-adenine dinucleotide, and the inactive analogue, pyridine-adenine dinucleotide to the enzyme horse liver alcohol dehydrogenase using X-ray crystallographic methods. These studies were made under such conditions that crystals of the complexes were isomorphous to apoenzyme crystals. Both analogues bind in the same conformation. The binding of the adenosine moiety is very similar to that of ADP-ribose or NADH bound to the enzyme. The conformation and mode of binding of the remaining portions of the analogue molecules is, however, quite different. The pyridine ring is not situated in the active-site pocket as the nicotinamide group in the isomorphous enzyme-NADH-imidazole complex but lies at the surface of the crevice between the two domains of the subunit, approximately 1.5 nm away from the catalytically active zinc atom. Lys-228 which has been shown to be important for NADH dissociation is in this region of the molecule.
D000429:Alcohol Oxidoreductases; D000818:Animals; D006736:Horses; D008099:Liver / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D008291:Malate Dehydrogenase; D008958:Models, Molecular; D008968:Molecular Conformation; D009243:NAD / Q000031:analogs & derivatives*; D011485:Protein Binding; D011487:Protein Conformation; D014961:X-Ray Diffraction
D009243:NAD; D000429:Alcohol Oxidoreductases; D008291:Malate Dehydrogenase