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Publication Abstract from PubMed

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.

A designed supramolecular protein assembly with in vivo enzymatic activity.,Song WJ, Tezcan FA Science. 2014 Dec 19;346(6216):1525-8. doi: 10.1126/science.1259680. PMID:25525249^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.