Conversion of the Coenzyme Specificity of Isocitrate Dehydrogenase by Module Replacement

Abstract
The coenzyme specificity of isocitrate dehydrogenase from an extreme thennophilic 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 modulereplaced 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.

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