Nature Chemical Biology 2012-11-01

Enzyme redesign guided by cancer-derived IDH1 mutations.

Zachary J Reitman, Bryan D Choi, Ivan Spasojevic, Darell D Bigner, John H Sampson, Hai Yan

Index: Nat. Chem. Biol. 8(11) , 887-9, (2012)

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Abstract

Mutations in an enzyme can result in a neomorphic catalytic activity in cancers. We applied cancer-associated mutations from isocitrate dehydrogenases to homologous residues in the active sites of homoisocitrate dehydrogenases to derive enzymes that catalyze the conversion of 2-oxoadipate to (R)-2-hydroxyadipate, a critical step for adipic acid production. Thus, we provide a prototypic example of how insights from cancer genome sequencing and functional studies can aid in enzyme redesign.