RETRACTED: Local Encoding of Computationally Designed Enzyme Activity

• Published in: Journal of molecular biology Vol. 366; no. 3; pp. 945 - 953
• Main Authors: Allert, Malin, Dwyer, Mary A., Hellinga, Homme W.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 23-02-2007
• Subjects: Escherichia coli; Thermoanaerobacter tengcongensis
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2006.12.002

This article has been retracted at the request of the authors and the Editor-in-Chief. Please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).
Reason: The recently reported gain of triose phosphate isomerase (TIM) activity in a mutant ribose-binding protein (RBP) from Thermoanaerobacter tengcongensis (tteNovoTIM) through the transplantation of mutants from a computationally designed mutant Escherichia coli RBP (ecNovoTIM) is incorrect. Dr. John P. Richard (Department of Chemistry, Department of Biochemistry, The State University of New York), to whom we provided clones of the ecNovoTIM and ttecNovoTIM mutants, has brought to our attention that reported acitivities observed in our reported preparations of both ecNovoTIM and tteNovoTIM can be attributed to a wild-type TIM impurity which separates from the mutant RBP peaks in preparations that use a continuous rather than step-wise imidazole gradient (as used in the reported work), or that add a second Sepharose column. Richard's reanalysis has been confirmed in the Hellinga laboratory. Our original interpretation of gain of activity in the tteNovoTIM mutant was based on the similarity of the observed TIM activity compared to the ecNovoTIM, and the apparent lack of activity in wild-type T. tengcongensis RBP purified under identical conditions as the engineered proteins. Unfortunately, the contaminating, endogenous TIM activity was not detected in this negative control.
We deeply regret that our reports of a designed enzyme activity do not live up to closer scrutiny. We offer our sincere apologies to all researchers whose work was negatively impacted by these reports. We remain optimistic that the problem of structure-based design of enzyme activity will be solved and that novel catalysts will be produced rationally by computational methods.