Enzyme redesign guided by cancer-derived IDH1 mutations.
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ABSTRACT:
SUBMITTER: Reitman ZJ
PROVIDER: S-EPMC3487689 | biostudies-literature | 2012 Nov
REPOSITORIES: biostudies-literature
Publications
Enzyme redesign guided by cancer-derived IDH1 mutations.
Reitman Zachary J ZJ Choi Bryan D BD Spasojevic Ivan I Bigner Darell D DD Sampson John H JH Yan Hai H
Nature chemical biology 20120923 11
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. ...[more]
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