Merck

Enzyme redesign guided by cancer-derived IDH1 mutations.

Nature chemical biology (2012-09-25)
Zachary J Reitman, Bryan D Choi, Ivan Spasojevic, Darell D Bigner, John H Sampson, Hai Yan
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Adipic acid, BioXtra, ≥99.5% (HPLC)
Sigma-Aldrich
Adipic acid, ≥99.5%
Sigma-Aldrich
Adipic acid, 99%
Supelco
Adipic acid, certified reference material, TraceCERT®
Sigma-Aldrich
2-Oxoadipic acid, ≥95.0% (HPLC)