Redesign of the coenzyme specificity of a dehydrogenase by protein engineering.

Nature · 1990

basic_science · Level V

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Abstract

Directed mutagenesis and molecular modelling have been used to identify a set of amino-acid side chains in glutathione reductase that confer specificity for the coenzyme NADP+. Systematic replacement of these amino acids, all of which occur in a 'fingerprint' structural motif in the NADP+-binding domain, leaves the substrate specificity unchanged but converts the enzyme into one displaying a marked preference for the coenzyme NAD+.