Differences in the oligomeric states of the LDH-like L-MalDH from the hyperthermophilic archaea Methanococcus jannaschii and Archaeoglobus fulgidus

L-Malate (MalDH) and L-lactate (LDH) dehydrogenases belong to the same fami ly of NAD-dependent enzymes. To gain insight into molecular relationships w ithin this family, we studied two hyperthermophilic (LDH-like) L-MalDH (pro teins with LDH-like structure and MalDH enzymatic activity) from the archae a Archaeoglobus fulgidus (Af) and Mehanococcus jannaschii (Mj). The structu ral parameters of these enzymes determined by neutron scattering and analyt ical centrifugation showed that the Af (LDH-like) L-MalDH is a dimer wherea s the Mj (LDH-like) L-MalDH is a tetramer. The effects of high temperature, cofactor binding, and high phosphate concentration were studied. They did not modify the oligomeric state of either enzyme. The enzymatic activity of the dimeric Af (LDH-like) L-MalDH is controlled by a pH-dependent transiti on at pH 7 without dissociation of the subunits. The data were analyzed in the light of the crystallographic structure of the LDH-like L-MalDH from Ha loarcula marismortui. This showed that a specific loop at the dimer-dimer c ontact regions in these enzymes controls the tetramer formation.