Nicotinamide adenine dinucleotide conformation

The model system that was used to demonstrate the reciprocal relations was adenosine-5 -mononicotinate, which is given in the stacked or interacted conformation in Fig. 6. The temperature effect for this molecule as seen in the circular dichroism spectra is given in Fig. 7, where the reciprocal relations are beautifully apparent. This approach has been used to identify stacked conformations for flavin-adenine dinucleotide and for the oxidized and reduced forms of a- and /3-nicotinamide-adenine dinucleotide. ... 

The enzyme lactate dehydrogenase, which catalyzes the transfer of electrons from lactate to NAD, illustrates these principles (Fig. 8.14). The coenzyme nicotinamide adenine dinucleotide (NAD ) is synthesized from the vitamin niacin (which forms the nicotinamide ring), and from ATP (which contributes an AMP). The ADP portion of the molecule binds tightly to the enzyme and causes conformational... 

Conformational specificity has been demonstrated by the coenzyme NADH (nicotinamide adenine dinucleotide) (12.41). Some apoenzymes that use this coenzyme remove only the axial (and others the equatorial) hydrogen atoms in the 4-position, as can readily be shown by replacing each of these atoms, in turn, by a deuterium atom. The absolute conformation of the labile hydrogen atoms in NADH were determined by Cornforth et al. (1962). 

The open conformation of NAD+ when bound to s-MDH is probably significantly different from the conformation in solution (72). Evidence from a number of NMR studies tend to indicate that in dilute aqueous solutions both NAD+ and NADH tend to have a folded conformation probably involving stacking of the adenine and nicotinamide bases (72-74). The folded form of the dinucleotide only represents a thermodynamic preference and intermediate unfolded configurations are also present (72). The presence of methanol or urea increases the preference of the dinucleotide for a more unfolded conformation (72). Differences in this conformational preference between NADH and NAD+ in the presence of urea and methanol have also been observed (72). The presence of methanol or urea may in fact mimic the environmental conditions in the active site of s-MDH. 

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