Crystal structure of sorbitol dehydrogenase.
Sorbitol dehydrogenase (SDH) is a distant relative to the alcohol dehydrogenases (ADHs) with sequence identities around 20%. SDH is a tetramer with one zinc ion per subunit. We have crystallized rat SDH and determined the structure by molecular replacement using a tetrameric bacterial ADH as search object. The conformation of the bound coenzyme is extended and similar to NADH bound to mammalian ADH but the interactions with the NMN-part have several differences with those of ADH. The active site zinc coordination in SDH is significantly different than in mammalian ADH but similar to the one found in the bacterial tetrameric NADP(H)-dependent ADH of Clostridiim beijerinckii. The substrate cleft is significantly more polar than for mammalian ADH and a number of residues are ideally located to position the sorbitol molecule in the active site. The SDH molecule can be considered to be a dimer of dimers, with subunits A-B and C-D, where the dimer interactions are similar 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 interactions, the tetramer-forming interactions are small with only few hydrogen bonds between side-chains.
Johansson
K
K
Department of Molecular Biology, Swedish University of Agricultural Sciences, S-751 24, Uppsala, Sweden.
El-Ahmad
M
M
Kaiser
C
C
Jörnvall
H
H
Eklund
H
H
Höög
J
J
Ramaswamy
S
S
D000818:Animals; D020134:Catalytic Domain; D003067:Coenzymes / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D066298:In Vitro Techniques; D007064:L-Iditol 2-Dehydrogenase / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D009243:NAD / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D021122:Protein Subunits; D051381:Rats; D013379:Substrate Specificity; D015032:Zinc / Q000737:chemistry
D003067:Coenzymes; D021122:Protein Subunits; D009243:NAD; D007064:L-Iditol 2-Dehydrogenase; D015032:Zinc