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Retraction of Dwyer et al., Science 304 (5679) 1967-1971.

Science 1 February 2008:
Vol. 319. no. 5863, p. 569
DOI: 10.1126/science.319.5863.569b
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Letters

Retraction

We wish to retract our Report "Computational design of a biologically active enzyme" (1), which describes triose phosphate isomerase activity in a computationally redesigned ribose-binding protein (RBP) from E. coli. Dr. John P. Richard (Department of Chemistry, Department of Biochemistry, The State University of New York at Buffalo), to whom we provided clones encoding the novoTIM activity, has brought to our attention that the triose phosphate isomerase activity observed in our reported preparations can be attributed to a wild-type TIM impurity--seen in preparations that use a continuous rather than stepwise imidazole gradient (as in the original paper) or that add a second sepharose column. Richard's reanalysis has now also been confirmed by others in the Hellinga laboratory. The interpretations in the original report were based on lack of observed activity in mutant, engineered enzyme that bound substrate, but lacked catalytic residues. Variations in expression levels of designed proteins relative to the amount of contaminating endogenous protein might account for the pattern of observed activities that led to our erroneous conclusions. The in vivo experiments have not been reexamined.

We deeply regret that our report of a designed enzyme activity does not live up to closer scrutiny. Nevertheless, we remain optimistic that the problem of structure-based design of enzyme activity will be solved and that novel catalysts will be produced in conjunction with computationally based methods.

Mary A. Dwyer
Department of Pharmacology and Cancer Biology
Duke University Medical Center
Durham, NC 27710, USA.

Loren L. Looger
Howard Hughes Medical Institute
Janelia Farm
Chevy Chase, MD 20815-6789, USA.

Homme W. Hellinga
Department of Biochemistry
Duke University Medical Center
Durham, NC 27710, USA.

Reference

  1. M. A. Dwyer, L. L. Looger, H. W. Hellinga, Science 304, 1967 (2004).


E-Letters:

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Comments on M. A. Dwyer et al. Retraction
Jack F. Kirsch
Science Online, 10 Mar 2008 [Full text]
Comment toward M. A. Dwyer et al. Retraction
John Richard
Science Online, 10 Mar 2008 [Full text]

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