Conversion of the coenzyme specificity of isocitrate dehydrogenase by module replacement.

The coenzyme specificity of isocitrate dehydrogenase from an extreme thermophilic bacterium was converted from NADP-dependent to NAD-dependent by replacing a "module" involved in the coenzyme binding site. The conversion was not possible with the replacement of a few residues that interact with the coenzyme. In addition, the module-replaced mutant dehydrogenase was as stable as the original, wild type enzyme. The results support a previous hypothesis that a module is a structural and functional unit of a protein.