Crystal structure of sorbitol dehydrogenase

Sorbitol dehydrogenase (SDH) is a distant relative to the alcohol dehydroge nases (ADHs) with sequence identities around 20%. SDH is a tetramer with on e zinc ion per subunit. We have crystallized rat SDH and determined the str ucture by molecular replacement using a tetrameric bacterial ADH as search object. The conformation of the bound coenzyme is extended and similar to N ADH bound to mammalian ADH but the interactions with the NMN-part have seve ral differences with those of ADH. The active site zinc coordination in SDH is significantly different than in mammalian ADH but similar to the one fo und in the bacterial tetrameric NADP(H)-dependent ADH of Clostridium beijer inckii. The substrate cleft is significantly more polar than for mammalian ADH and a number of residues are ideally located to position the sorbitol m olecule in the active site. The SDH molecule can be considered to be a dime r of dimers, with subunits A-B and C-D, where the dimer interactions are si milar to those in mammalian ADH. The tetramers are composed of two of these dimers, which interact with their surfaces opposite the active site clefts , which are accessible on the opposite side. In contrast to the dimer inter actions, the tetramer-forming interactions are small with only few hydrogen bonds between side-chains. (C) 2001 Elsevier Science Ireland Ltd. All righ ts reserved.