EFFECT OF DIMETHYL SULFOXIDE ON ALLOSTERIC TRANSITIONS OF GLUTAMIC DEHYDROGENASE

The modification of the allosteric transitions of bovine liver glutamic dehydrogenase (GDH) [l-glutamate:NAD(P) oxidoreductase (deaminating) EC 1.4.1.3] by heavy water (D2O) led to the investigation of the effects of a second solvent, dimethyl sulfoxide (DMSO), on GDH. DMSO resembles D2O in that it replaces bound water in proteins and also forms stronger hydrogen bonds than water. DMSO was found to induce or facilitate the conversion of the active monomer into the inactive monomer and to stabilize the inactive monomer against irreversible denaturation into individual subunits. DMSO decreased the ability of ADP to stimulate GDH and increased the ability of GTP to inhibit the enzyme. These results suggest that the inactive monomer of GDH may have more hydrophilic groups on the surface of the protein available for hydrogen bonding with solvents such as DMSO or D2O and hence is favored in the presence of these solvents. The ability of the aprotic solvent DMSO to compete with the protein for proton-donor groups to form hydrogen bonds may explain the apparent dissociation of polymeric aggregates observed in the presence of low levels of DMSO. © 1969.