2dte | pdb_00002dte
Structure of Thermoplasma acidophilum aldohexose dehydrogenase (AldT) in complex with NADH
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. Structural insights into unique substrate selectivity of Thermoplasma acidophilum D-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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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