2cda | pdb_00002cda
Sulfolobus solfataricus Glucose Dehydrogenase 1 in complex with NADP
Structural highlights
Function[GLCDH_SULSF] Catalyzes the NAD(P)(+)-dependent oxidation of D-glucose to D-gluconate via gluconolactone. Displays broad substrate specificity since it is able to catalyze the oxidation of a number of alternative aldose sugars, such as D-galactose, D-xylose and L-arabinose, to the corresponding glyconate. Can utilize both NAD(+) and NADP(+) as electron acceptor. Physiologically, seems to be involved in the degradation of both glucose and galactose through a non-phosphorylative variant of the Entner-Doudoroff pathway.[1] [2] 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 hyperthermophilic archaeon Sulfolobus solfataricus grows optimally above 80 degrees C and utilizes an unusual, promiscuous, non-phosphorylative Entner-Doudoroff pathway to metabolize both glucose and galactose. The first enzyme in this pathway, glucose dehydrogenase, catalyzes the oxidation of glucose to gluconate, but has been shown to have activity with a broad range of sugar substrates, including glucose, galactose, xylose, and L-arabinose, with a requirement for the glucose stereo configuration at the C2 and C3 positions. Here we report the crystal structure of the apo form of glucose dehydrogenase to a resolution of 1.8 A and a complex with its required cofactor, NADP+, to a resolution of 2.3 A. A T41A mutation was engineered to enable the trapping of substrate in the crystal. Complexes of the enzyme with D-glucose and D-xylose are presented to resolutions of 1.6 and 1.5 A, respectively, that provide evidence of selectivity for the beta-anomeric, pyranose form of the substrate, and indicate that this is the productive substrate form. The nature of the promiscuity of glucose dehydrogenase is also elucidated, and a physiological role for this enzyme in xylose metabolism is suggested. Finally, the structure suggests that the mechanism of sugar oxidation by this enzyme may be similar to that described for human sorbitol dehydrogenase. The structural basis of substrate promiscuity in glucose dehydrogenase from the hyperthermophilic archaeon Sulfolobus solfataricus.,Milburn CC, Lamble HJ, Theodossis A, Bull SD, Hough DW, Danson MJ, Taylor GL J Biol Chem. 2006 May 26;281(21):14796-804. Epub 2006 Mar 23. PMID:16556607[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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