Liver alcohol dehydrogenase NADH binding

A crystal structure of a ternary complex of horse liver alcohol dehydrogenase with NADH and the inhibitor, dimethyl sulfoxide, first at 4.5 A resolution1365 and a further refinement to 2.9 A resolution,1366 has been published by Eklund et al. The gross structure of the ternary complex is similar to that of the free enzyme structure. Each subunit is divided into a coenzyme-binding domain and a catalytic domain. The subunits are joined together near the... 

Fig. 32. Horse liver alcohol dehydrogenase. The full line shows positions in the apo-enzyme (Fig. 30) and the broken line shows positions in the ternary complex with NADH and dimethyl sulphoxide (Fig. 31). This figure therefore illustrates the movement of active site residues that occurs when the coenzyme and substrate analogue bind. Stereo drawing from the work of Branden and colleagues. 

The mechanism of this oxidation for the enzyme liver alcohol dehydrogenase is shown for the reaction of 83, where ethanol is bound to the active site of the enzyme to give 84 via proton abstraction and then hydride transfer to generate acetaldehyde (see 85). NAD+ binds to the active site of the enzyme to induce a conformational change (see Chapter 8 for conformation) to close the active site. The oxidation of ethanol to acetaldehyde (ethanal) is accompanied by reduction of NAD+ to NADH, as shown in the illustration. 

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