Crystal structure of an archaeal class I aldolase and the evolution of (betaalpha)8 barrel proteins.
Fructose-1,6-bisphosphate aldolase (FBPA) catalyzes the reversible cleavage of fructose 1,6-bisphosphate to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate in the glycolytic pathway. FBPAs from archaeal organisms have recently been identified and characterized as a divergent family of proteins. Here, we report the first crystal structure of an archaeal FBPA at 1.9-A resolution. The structure of this 280-kDa protein complex was determined using single wavelength anomalous dispersion followed by 10-fold non-crystallographic symmetry averaging and refined to an R-factor of 14.9% (Rfree 17.9%). The protein forms a dimer of pentamers, consisting of subunits adopting the ubiquitous (betaalpha)8 barrel fold. Additionally, a crystal structure of the archaeal FBPA covalently bound to dihydroxyacetone phosphate was solved at 2.1-A resolution. Comparison of the active site residues with those of classical FBPAs, which share no significant sequence identity but display the same overall fold, reveals a common ancestry between these two families of FBPAs. Structural comparisons, furthermore, establish an evolutionary link to the triosephosphate isomerases, a superfamily hitherto considered independent from the superfamily of aldolases.
Lorentzen
Esben
E
European Molecular Biology Laboratory, Hamburg Outstation, Notkestrasse 85, D-22603 Hamburg, Germany.
Pohl
Ehmke
E
Zwart
Peter
P
Stark
Alexander
A
Russell
Robert B
RB
Knura
Thomas
T
Hensel
Reinhard
R
Siebers
Bettina
B
D019843:Archaeal Proteins / Q000737:chemistry*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004099:Dihydroxyacetone Phosphate / Q000737:chemistry; D019143:Evolution, Molecular; D005634:Fructose-Bisphosphate Aldolase / Q000737:chemistry*; D015394:Molecular Structure; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry; D019624:Thermoproteaceae / Q000201:enzymology
D019843:Archaeal Proteins; D021122:Protein Subunits; D004099:Dihydroxyacetone Phosphate; D005634:Fructose-Bisphosphate Aldolase