The Conformation of Adenosine Diphosphoribose and 8‐Bromoadenosine Diphosphoribose when Bound to Liver Alcohol Dehydrogenase

Abstract

8‐Bromo‐adenosine diphosphoribose (br8 ADP‐Rib) and nicotinamide 8‐bromoadenine dinucleotide (Nbr8AD+) which are analogues of the coenzyme NAD+, were prepared and their liver alcohol dehydrogenase complexes studied by crystallographic methods. Nbr8AD+ is active in hydrogen transport and br8ADP‐Rib is a coenzyme competitive inhibitor for the enzymes liver alcohol dehydrogenase and yeast alcohol dehydrogenase. X‐ray data were obtained for the complex between liver alcohol dehydrogenase and br8 ADP‐Rib to 0.45 nm resolution and for the liver alcohol dehydrogenase‐adenosine diphosphoribose complex to 0.29‐nm resolution. The conformations of these analogues were determined from the X‐ray data. It was found that ADP‐Rib had a conformation very similar to the corresponding part of NAD+, when NAD+ is bound to lactate and malate dehydrogenase. br8 ADP‐Rib had the same anti conformation of the adenine ring with respect to the ribose as ADP‐Rib and NAD+, in contrast to the syn conformation found in 8‐bromo‐adenosine. The overcrowding at the 8‐position is relieved in br8ADP‐Rib by having the ribose in the 2′endo conformation instead of the usual 3′endo as in ADP‐Rib and NAD+. Copyright © 1975, Wiley Blackwell. All rights reserved