Computational design of a biologically active enzyme.

@article{citeulike:384589, 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.}, address = {Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.}, author = {Dwyer, M. A. and Looger, L. L. and Hellinga, H. W. }, citeulike-article-id = {384589}, doi = {10.1126/science.1098432}, issn = {1095-9203}, journal = {Science}, keywords = {protein\_design, synthetic\_biology}, month = {June}, number = {5679}, pages = {1967--1971}, posted-at = {2008-01-31 19:32:45}, priority = {2}, title = {Computational design of a biologically active enzyme.}, url = {http://dx.doi.org/10.1126/science.1098432}, volume = {304}, year = {2004} }

TY - JOUR ID - citeulike:384589 L3 - citeulike-article-id:384589 TI - Computational design of a biologically active enzyme. JF - Science VL - 304 IS - 5679 SP - 1967 EP - 1971 AD - Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA. SN - 1095-9203 N2 - 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. KW - protein_design KW - synthetic_biology AU - Dwyer, MA AU - Looger, LL AU - Hellinga, HW PY - 2004/06/25/ UR - http://dx.doi.org/10.1126/science.1098432 ER -