Computational design of a biologically active enzyme.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Dwyer, MA; Looger, LL; Hellinga, HW

Published Date

  • June 25, 2004

Published In

Volume / Issue

  • 304 / 5679

Start / End Page

  • 1967 - 1971

PubMed ID

  • 15218149

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.1098432


  • eng

Conference Location

  • United States