FORMYLMETHANOFURAN - TETRAHYDROMETHANOPTERIN FORMYLTRANSFERASE FROM METHANOPYRUS-KANDLERI - NEW INSIGHTS INTO SALT-DEPENDENCE AND THERMOSTABILITY

Background: Formylmethanofuran: tetrahydromethanopterin formyltransfer ase (Ftr) from the methanogenic Archaeon Methanopyrus kandleri (optimu m growth temperature 98 degrees C) is a hyperthermophilic enzyme that is absolutely dependent on the presence of lyotropic salts for activit y and thermostability. The enzyme is involved in the pathway of carbon dioxide reduction to methane and catalyzes the transfer of formyl fro m formylmethanofuran to tetrahydromethanopterin.Results: The crystal s tructure of Ftr, determined to a resolution of 1.73 Angstrom, reveals a homotetramer composed essentially of two dimers. Each subunit is sub divided into two tightly associated lobes both consisting of a predomi nantly antiparallel beta sheet flanked by a helices forming an alpha/b eta sandwich structure. The approximate location of the active site wa s detected in a region close to the dimer interface. Conclusions: The adaptation of Ftr against high lyotropic salt concentrations is struct urally reflected by a large number of negatively charged residues and their high local concentration on the surface of the protein. The salt -dependent thermostability of Ftr might be explained on a molecular ba sis by ionic interactions at the protein surface, involving both prote in and inorganic salt ions, and the mainly hydrophobic interactions be tween the subunits and within the core.