Precision is essential for efficient catalysis in an evolved Kemp eliminase

Blomberg, Rebecca; Kries, Hajo; Pinkas, Daniel M.; Mittl, Peer R. E.; Grütter, Markus G.; Privett, Heidi K.; Mayo, Stephen L.; Hilvert, Donald

doi:10.1038/nature12623

Publication type:	Article in scientific journal
Type of review:	Peer review (publication)
Title:	Precision is essential for efficient catalysis in an evolved Kemp eliminase
Authors:	Blomberg, Rebecca Kries, Hajo Pinkas, Daniel M. Mittl, Peer R. E. Grütter, Markus G. Privett, Heidi K. Mayo, Stephen L. Hilvert, Donald
DOI:	10.1038/nature12623
Published in:	Nature
Volume(Issue):	503
Issue:	7476
Page(s):	418
Pages to:	421
Issue Date:	2013
Publisher / Ed. Institution:	Nature Publishing Group
ISSN:	0028-0836 1476-4687
Language:	English
Subjects:	Carbon; Catalytic domain; X-ray crystallography; Enzymes; Kinetics; Molecular models; Protons; Triazoles; Triose-phosphate isomerase; Biocatalysis; Directed molecular evolution; Protein engineering
Subject (DDC):	660.6: Biotechnology
Abstract:	Linus Pauling established the conceptual framework for understanding and mimicking enzymes more than six decades ago. The notion that enzymes selectively stabilize the rate-limiting transition state of the catalysed reaction relative to the bound ground state reduces the problem of design to one of molecular recognition. Nevertheless, past attempts to capitalize on this idea, for example by using transition state analogues to elicit antibodies with catalytic activities, have generally failed to deliver true enzymatic rates. The advent of computational design approaches, combined with directed evolution, has provided an opportunity to revisit this problem. Starting from a computationally designed catalyst for the Kemp elimination--a well-studied model system for proton transfer from carbon – we show that an artificial enzyme can be evolved that accelerates an elementary chemical reaction 6 × 10(8)-fold, approaching the exceptional efficiency of highly optimized natural enzymes such as triosephosphate isomerase. A 1.09 Å resolution crystal structure of the evolved enzyme indicates that familiar catalytic strategies such as shape complementarity and precisely placed catalytic groups can be successfully harnessed to afford such high rate accelerations, making us optimistic about the prospects of designing more sophisticated catalysts.
URI:	https://digitalcollection.zhaw.ch/handle/11475/9661
Fulltext version:	Published version
License (according to publishing contract):	Licence according to publishing contract
Departement:	Life Sciences and Facility Management
Organisational Unit:	Institute of Chemistry and Biotechnology (ICBT)
Appears in collections:	Publikationen Life Sciences und Facility Management

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Blomberg, R., Kries, H., Pinkas, D. M., Mittl, P. R. E., Grütter, M. G., Privett, H. K., Mayo, S. L., & Hilvert, D. (2013). Precision is essential for efficient catalysis in an evolved Kemp eliminase. Nature, 503(7476), 418–421. https://doi.org/10.1038/nature12623

Blomberg, R. et al. (2013) ‘Precision is essential for efficient catalysis in an evolved Kemp eliminase’, Nature, 503(7476), pp. 418–421. Available at: https://doi.org/10.1038/nature12623.

R. Blomberg et al., “Precision is essential for efficient catalysis in an evolved Kemp eliminase,” Nature, vol. 503, no. 7476, pp. 418–421, 2013, doi: 10.1038/nature12623.

BLOMBERG, Rebecca, Hajo KRIES, Daniel M. PINKAS, Peer R. E. MITTL, Markus G. GRÜTTER, Heidi K. PRIVETT, Stephen L. MAYO und Donald HILVERT, 2013. Precision is essential for efficient catalysis in an evolved Kemp eliminase. Nature. 2013. Bd. 503, Nr. 7476, S. 418–421. DOI 10.1038/nature12623

Blomberg, Rebecca, Hajo Kries, Daniel M. Pinkas, Peer R. E. Mittl, Markus G. Grütter, Heidi K. Privett, Stephen L. Mayo, and Donald Hilvert. 2013. “Precision Is Essential for Efficient Catalysis in an Evolved Kemp Eliminase.” Nature 503 (7476): 418–21. https://doi.org/10.1038/nature12623.

Blomberg, Rebecca, et al. “Precision Is Essential for Efficient Catalysis in an Evolved Kemp Eliminase.” Nature, vol. 503, no. 7476, 2013, pp. 418–21, https://doi.org/10.1038/nature12623.