title: Crystal structure of an archaeal class I aldolase and the evolution of (betaalpha)8 barrel proteins.
abstract: 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.
authors.affiliation: European Molecular Biology Laboratory, Hamburg Outstation, Notkestrasse 85, D-22603 Hamburg, Germany.
authors.forename: Esben
authors.initials: E
authors.lastname: Lorentzen
authors.forename: Ehmke
authors.initials: E
authors.lastname: Pohl
authors.forename: Peter
authors.initials: P
authors.lastname: Zwart
authors.forename: Alexander
authors.initials: A
authors.lastname: Stark
authors.forename: Robert B
authors.initials: RB
authors.lastname: Russell
authors.forename: Thomas
authors.initials: T
authors.lastname: Knura
authors.forename: Reinhard
authors.initials: R
authors.lastname: Hensel
authors.forename: Bettina
authors.initials: B
authors.lastname: Siebers
mesh_terms: 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
chemical_list: D019843:Archaeal Proteins; D021122:Protein Subunits; D004099:Dihydroxyacetone Phosphate; D005634:Fructose-Bisphosphate Aldolase