5-Methylnicotinamide-adenine dinucleotide. Kinetic investigation with major and minor isoenzymes of liver alcohol dehydrogenase and structural determination of its binary complex with alcohol dehydrogenase.
5-Methylnicotinamide-adenine dinucleotide and 3-cyano-5-methylpyridine-adenine dinucleotide was prepared from 5-methylthionicotinamide-adenine dinucleotide by chemical conversion. The 5-methylthionicotinamide-adenine dinucleotide was obtained by enzymic transglucosidation. Model compounds ascertained the structure. None of the dinucleotides methylated at C-5 was active with the major isoenzyme EE of horse liver alcohol dehydrogenase, but activity with 5-methylnicotinamide-adenine dinucleotide was measured with the minor isoenzymes. The binding of 5-methylnicotinamide-adenine dinucleotide to liver alcohol dehydrogenase, investigated by X-ray diffraction methods to 0.37-nm resolution, occurs with the pyridinium ring away from the active site as previously described for 3-iodopyridine-adenine and pyridine-adenine dinucleotides. A general conclusion on the use of inhibitors as tools for exploration of the active site is drawn.
D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D055598:Chemical Phenomena; D002621:Chemistry; D006736:Horses; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008958:Models, Molecular; D009243:NAD / Q000031:analogs & derivatives* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013552:Swine; D014961:X-Ray Diffraction
D007527:Isoenzymes; D009243:NAD; C032641:5-methylnicotinamide-adenine dinucleotide; D000429:Alcohol Oxidoreductases