RETRACTED: Computational design of a biologically active enzyme (Retracted article. See vol 319, pg 569, 2008)

被引:235
作者
Dwyer, MA [1 ]
Looger, LL [1 ]
Hellinga, HW [1 ]
机构
[1] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA
关键词
D O I
10.1126/science.1098432
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:1967 / 1971
页数:5
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