2dtd
Structure of Thermoplasma acidophilum aldohexose dehydrogenase (AldT) in ligand-free form
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OverviewOverview
The d-aldohexose dehydrogenase from the thermoacidophilic archaea, Thermoplasma acidophilum (AldT) belongs to the short-chain, dehydrogenase/reductase (SDR) superfamily and catalyzes the oxidation of, several monosaccharides with a preference for NAD(+) rather than NADP(+), as a cofactor. It has been found that AldT is a unique enzyme that, exhibits the highest dehydrogenase activity against d-mannose. Here, we, describe the crystal structures of AldT in ligand-free form, in complex, with NADH, and in complex with the substrate d-mannose, at 2.1 A, 1.65 A, and 1.6 A resolution, respectively. The AldT subunit forms a typical SDR, fold with an unexpectedly long C-terminal tail and assembles into an, intertwined tetramer. The d-mannose complex structure reveals that Glu84, interacts with the axial C2 hydroxyl group of the bound d-mannose., Structural comparison with Bacillus megaterium glucose dehydrogenase, (BmGlcDH) suggests that the conformation of the glutamate side-chain is, crucial for discrimination between d-mannose and its C2 epimer d-glucose, and the conformation of the glutamate side-chain depends on the spatial, arrangement of nearby hydrophobic residues that do not directly interact, with the substrate. Elucidation of the d-mannose recognition mechanism of, AldT further provides structural insights into the unique substrate, selectivity of AldT. Finally, we show that the extended C-terminal tail, completely shuts the substrate-binding pocket of the neighboring subunit, both in the presence and absence of substrate. The elaborate inter-subunit, interactions between the C-terminal tail and the entrance of the, substrate-binding pocket imply that the tail may play a pivotal role in, the enzyme activity.
About this StructureAbout this Structure
2DTD is a Single protein structure of sequence from Thermoplasma acidophilum with as ligand. Active as Glucose 1-dehydrogenase (NAD(+)), with EC number 1.1.1.118 Full crystallographic information is available from OCA.
ReferenceReference
Structural Insights into Unique Substrate Selectivity of Thermoplasma acidophilumd-Aldohexose Dehydrogenase., Yasutake Y, Nishiya Y, Tamura N, Tamura T, J Mol Biol. 2007 Apr 6;367(4):1034-46. Epub 2007 Jan 16. PMID:17300803
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