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- Title
Computational design of a biologically active enzyme.
- Authors
Dwyer, Mary A; Looger, Loren L; Hellinga, Homme W
- Abstract
Rational design of enzymes is a stringent test of our understanding of protein chemistry and has numerous potential applications. Here, we present and experimentally validate the computational design of enzyme activity in proteins of known structure. We have predicted mutations that introduce triose phosphate isomerase activity into ribose-binding protein, a receptor that normally lacks enzyme activity. The resulting designs contain 18 to 22 mutations, exhibit 10(5)- to 10(6)-fold rate enhancements over the uncatalyzed reaction, and are biologically active, in that they support the growth of Escherichia coli under gluconeogenic conditions. The inherent generality of the design method suggests that many enzymes can be designed by this approach.
- Publication
Science (New York, N.Y.), 2004, Vol 304, Issue 5679, p1967
- ISSN
1095-9203
- Publication type
Journal Article
- DOI
10.1126/science.1098432