Robust design and optimization of retroaldol enzymes.
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ABSTRACT:
SUBMITTER: Althoff EA
PROVIDER: S-EPMC3403469 | biostudies-literature | 2012 May
REPOSITORIES: biostudies-literature
Publications
Robust design and optimization of retroaldol enzymes.
Althoff Eric A EA Wang Ling L Jiang Lin L Giger Lars L Lassila Jonathan K JK Wang Zhizhi Z Smith Matthew M Hari Sanjay S Kast Peter P Herschlag Daniel D Hilvert Donald D Baker David D
Protein science : a publication of the Protein Society 20120330 5
Enzyme catalysts of a retroaldol reaction have been generated by computational design using a motif that combines a lysine in a nonpolar environment with water-mediated stabilization of the carbinolamine hydroxyl and β-hydroxyl groups. Here, we show that the design process is robust and repeatable, with 33 new active designs constructed on 13 different protein scaffold backbones. The initial activities are not high but are increased through site-directed mutagenesis and laboratory evolution. Mut ...[more]
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