Crystal structure of an archaeal class I aldolase and the evolution of (betaalpha)8 barrel proteins

J Biol Chem. 2003 Nov 21;278(47):47253-60. doi: 10.1074/jbc.M305922200. Epub 2003 Aug 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Archaeal Proteins / chemistry*
  • Binding Sites
  • Crystallography, X-Ray
  • Dihydroxyacetone Phosphate / chemistry
  • Evolution, Molecular*
  • Fructose-Bisphosphate Aldolase / chemistry*
  • Molecular Structure
  • Protein Conformation
  • Protein Subunits / chemistry
  • Thermoproteaceae / enzymology


  • Archaeal Proteins
  • Protein Subunits
  • Dihydroxyacetone Phosphate
  • Fructose-Bisphosphate Aldolase

Associated data

  • PDB/1OJX
  • PDB/1OK4
  • PDB/1OK6