Publikationstyp: Beitrag in wissenschaftlicher Zeitschrift
Art der Begutachtung: Peer review (Publikation)
Titel: Precision is essential for efficient catalysis in an evolved Kemp eliminase
Autor/-in: 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
Erschienen in: Nature
Band(Heft): 2013
Heft: 503
Seite(n): 418
Seiten bis: 421
Erscheinungsdatum: 2013
Verlag / Hrsg. Institution: Springer
ISSN: 0028-0836
Sprache: Englisch
Schlagwörter: Carbon; Catalytic domain; X-ray crystallography; Enzymes; Kinetics; Molecular models; Protons; Triazoles; Triose-phosphate isomerase; Biocatalysis; Directed molecular evolution; Protein engineering
Fachgebiet (DDC): 660.6: Biotechnologie
Zusammenfassung: 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.
Volltext Version: Publizierte Version
Lizenz (gemäss Verlagsvertrag): Lizenz gemäss Verlagsvertrag
Departement: Life Sciences und Facility Management
Organisationseinheit: Institut für Chemie und Biotechnologie (ICBT)
Enthalten in den Sammlungen:Publikationen Life Sciences und Facility Management

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