Crystal structures and enzymatic properties of three formyltransferases from archaea: environmental adaptation and evolutionary relationship

Protein Sci. 2002 Sep;11(9):2168-78. doi: 10.1110/ps.0211002.


Formyltransferase catalyzes the reversible formation of formylmethanofuran from N(5)-formyltetrahydromethanopterin and methanofuran, a reaction involved in the C1 metabolism of methanogenic and sulfate-reducing archaea. The crystal structure of the homotetrameric enzyme from Methanopyrus kandleri (growth temperature optimum 98 degrees C) has recently been solved at 1.65 A resolution. We report here the crystal structures of the formyltransferase from Methanosarcina barkeri (growth temperature optimum 37 degrees C) and from Archaeoglobus fulgidus (growth temperature optimum 83 degrees C) at 1.9 A and 2.0 A resolution, respectively. Comparison of the structures of the three enzymes revealed very similar folds. The most striking difference found was the negative surface charge, which was -32 for the M. kandleri enzyme, only -8 for the M. barkeri enzyme, and -11 for the A. fulgidus enzyme. The hydrophobic surface fraction was 50% for the M. kandleri enzyme, 56% for the M. barkeri enzyme, and 57% for the A. fulgidus enzyme. These differences most likely reflect the adaptation of the enzyme to different cytoplasmic concentrations of potassium cyclic 2,3-diphosphoglycerate, which are very high in M. kandleri (>1 M) and relatively low in M. barkeri and A. fulgidus. Formyltransferase is in a monomer/dimer/tetramer equilibrium that is dependent on the salt concentration. Only the dimers and tetramers are active, and only the tetramers are thermostable. The enzyme from M. kandleri is a tetramer, which is active and thermostable only at high concentrations of potassium phosphate (>1 M) or potassium cyclic 2,3-diphosphoglycerate. Conversely, the enzyme from M. barkeri and A. fulgidus already showed these properties, activity and stability, at much lower concentrations of these strong salting-out salts.

MeSH terms

  • Archaeoglobus fulgidus / enzymology*
  • Crystallography, X-Ray
  • Environment
  • Euryarchaeota / enzymology*
  • Evolution, Molecular*
  • Hydroxymethyl and Formyl Transferases / chemistry*
  • Hydroxymethyl and Formyl Transferases / classification
  • Hydroxymethyl and Formyl Transferases / genetics
  • Hydroxymethyl and Formyl Transferases / metabolism*
  • Methanosarcina barkeri / enzymology*
  • Models, Molecular
  • Phylogeny
  • Protein Structure, Quaternary
  • Protein Subunits
  • Temperature
  • Ultracentrifugation


  • Protein Subunits
  • Hydroxymethyl and Formyl Transferases

Associated data

  • PDB/1M5H
  • PDB/1M5S