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A designed supramolecular protein assembly with in vivo enzymatic activity
Cited 205 time in
Web of Science
Cited 217 time in Scopus
- Authors
- Issue Date
- 2014-12
- Citation
- Science, Vol.346 No.6216, pp.1525-1528
- Abstract
- The generation of new enzymatic activities has mainly relied on repurposing the interiors of preexisting protein folds because of the challenge in designing functional, three-dimensional protein structures from first principles. Here we report an artificial metallo-beta-lactamase, constructed via the self-assembly of a structurally and functionally unrelated, monomeric redox protein into a tetrameric assembly that possesses catalytic zinc sites in its interfaces. The designed metallo-beta-lactamase is functional in the Escherichia coli periplasm and enables the bacteria to survive treatment with ampicillin. In vivo screening of libraries has yielded a variant that displays a catalytic proficiency [(k(cat)/K-m)/k(uncat)] for ampicillin hydrolysis of 2.3 x 10(6) and features the emergence of a highly mobile loop near the active site, a key component of natural beta-lactamases to enable substrate interactions.
- ISSN
- 0036-8075
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