The crystal structure of glucose dehydrogenase from Thermoplasma acidophilum.
BACKGROUND
The archaea are a group of organisms distinct from bacteria and eukaryotes. Structures of proteins from archaea are of interest because they function in extreme environments and because structural studies may reveal evolutionary relationships between proteins. The enzyme glucose dehydrogenase from the thermophilic archaeon Thermoplasma acidophilum is of additional interest because it is involved in an unusual pathway of sugar metabolism.


RESULTS
We have determined the crystal structure of this glucose dehydrogenase to 2.9 A resolution. The monomer comprises a central nucleotide-binding domain, common to other nucleotide-binding dehydrogenases, flanked by the catalytic domain. Unexpectedly, we observed significant structural homology between the catalytic domain of horse liver alcohol dehydrogenase and T. acidophilum glucose dehydrogenase.


CONCLUSIONS
The structural homology between glucose dehydrogenase and alcohol dehydrogenase suggests an evolutionary relationship between these enzymes. The quaternary structure of glucose dehydrogenase may provide a model for other tetrameric alcohol/polyol dehydrogenases. The predicted mode of nucleotide binding provides a plausible explanation for the observed dual-cofactor specificity, the molecular basis of which can be tested by site-directed mutagenesis.
John
J
J
School of Biology and Biochemistry, Bath University, UK.
Crennell
S J
SJ
Hough
D W
DW
Danson
M J
MJ
Taylor
G L
GL
D000426:Alcohol Dehydrogenase / Q000737:chemistry; D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D042843:Glucose 1-Dehydrogenase; D005948:Glucose Dehydrogenases / Q000737:chemistry* / Q000378:metabolism; D007064:L-Iditol 2-Dehydrogenase / Q000737:chemistry; D008667:Metalloproteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D013822:Thermoplasma / Q000201:enzymology*; D015032:Zinc / Q000737:chemistry
D008667:Metalloproteins; D009243:NAD; D009249:NADP; D005948:Glucose Dehydrogenases; D000426:Alcohol Dehydrogenase; D007064:L-Iditol 2-Dehydrogenase; D042843:Glucose 1-Dehydrogenase; D015032:Zinc