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

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Abstract
5-Methylnicotinamide-adenine dinucleotide (m5NAD+) and 3-cyano-5-methylpyridine-adenine dinucleotide were prepared from 5-methylthionicotinamide-adenine dinucleotide (m5sNAD+) by chemical conversion. m5sNAD+ 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 m5NAD+ was measured with the minor isoenzymes. The binding of m5NAD+ to liver alcohol dehydrogenase, investigated by X-ray diffraction methods to 0.37 nm resolution, occurs with 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.