ArticleProceedings of the National Academy of Sciences of the United States of America1999
Rational design of a scytalone dehydratase-like enzyme using a structurally homologous protein scaffold.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 31 citations in OpenAlex.
- Enzyme (re)design: lessons from natural evolution and computation.Current opinion in chemical biology · 2009Review
- Incorporation of a single His residue by rational design enables thiol-ester hydrolysis by human glutathione transferase A1-1.Proceedings of the National Academy of Sciences of the United States of America · 2004Article
- Enzyme-like proteins by computational design.Proceedings of the National Academy of Sciences of the United States of America · 2001Article
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4 authors at 1 institution in 1 country.
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Abstract
The generation of enzymes to catalyze specific reactions is one of the more challenging problems facing protein engineers. Structural similarities between the enzyme scytalone dehydratase with nuclear transport factor 2 (NTF2) suggested the potential for NTF2 to be re-engineered into a scytalone dehydratase-like enzyme. We introduced four key catalytic residues into NTF2 to create a scytalone dehydratase-like active site. A C-terminal helix found in scytalone dehydratase but absent in NTF2 also was added. Mutant NTF2 proteins were tested for catalytic activity by using a spectroscopic assay. One of the engineered enzymes exhibited catalytic activity with minimal kcat and Km values of 0.125 min-1 and 800 microM, respectively. This level of catalytic activity represents minimally a 150-fold improvement in activity over the background rate for substrate dehydration and a dramatic step forward from the catalytically inert parent NTF2. This work represents one of the few examples of converting a protein scaffold into an enzyme, outside those arising from the induction of catalytic activity into antibodies.
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