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Crystal structure of sorbitol dehydrogenase
K Johansson1, M El-Ahmad, C Kaiser
1Department of Molecular Biology, Swedish University of Agricultural Sciences, S-751 24, Uppsala, Sweden.
Chemico-Biological Interactions
|April 18, 2001
Summary
Sorbitol dehydrogenase (SDH) structure reveals distinct zinc coordination and a polar active site, differing from alcohol dehydrogenases (ADHs). This study elucidates SDH
Area of Science:
- Biochemistry
- Structural Biology
- Enzymology
Background:
- Sorbitol dehydrogenase (SDH) is structurally related to alcohol dehydrogenases (ADHs).
- SDH functions as a tetramer, with each subunit binding a zinc ion.
Purpose of the Study:
- To determine the crystal structure of rat sorbitol dehydrogenase.
- To compare the structural features of SDH with those of ADHs, particularly regarding coenzyme binding and active site architecture.
Main Methods:
- Crystallization of rat sorbitol dehydrogenase.
- Structure determination using molecular replacement with a bacterial ADH template.
- Analysis of coenzyme conformation and active site zinc coordination.
Main Results:
- The determined structure reveals an extended conformation of the bound coenzyme, NADH, with unique interactions in the NMN-part compared to ADH.
- SDH exhibits distinct zinc coordination in its active site, resembling bacterial NADP(H)-dependent ADH more than mammalian ADH.
- The substrate cleft of SDH is more polar than that of mammalian ADH, with residues positioned to facilitate sorbitol binding.
- SDH forms a dimer of dimers, with tetramerization interfaces involving minimal inter-subunit contacts.
Conclusions:
- The crystal structure provides insights into the catalytic mechanism and substrate specificity of SDH.
- SDH's structural characteristics highlight its unique evolutionary relationship within the ADH superfamily.