Report

Computational Design of a Biologically Active Enzyme

Science  25 Jun 2004:
Vol. 304, Issue 5679, pp. 1967-1971
DOI: 10.1126/science.1098432

You are currently viewing the abstract.

View Full Text
As a service to the community, AAAS/Science has made this article free with registration.

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 105- to 106-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.

    View Full Text

    Cited By...