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Changing the Cofactor Diet of an Enzyme

In all life, NADis the cofactor for an enzyme used in leucine biosynthesis. In their Perspective,
 Ellington and Bull
 discuss how a five-amino acid change in the enzyme switches the cofactor to NADP, with normal activity in vitro. Yet NADPuse in vivo comes at an unavoidable cost, explaining the conservation of cofactor specificities in natural enzymes.