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The evolution of mu...
The evolution of multiple active site configurations in a designed enzyme
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- Hong, Nan-Sook (author)
- Australian Natl Univ, Res Sch Chem, Canberra, ACT 2601, Australia
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- Petrovic, Dusan (author)
- Uppsala universitet,Biokemi
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- Lee, Richmond (author)
- Australian Natl Univ, Res Sch Chem, Canberra, ACT 2601, Australia
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- Gryn'ova, Ganna (author)
- Australian Natl Univ, Res Sch Chem, Canberra, ACT 2601, Australia;Ecole Polytech Fed Lausanne, Inst Sci & Ingn Chim, CH-1015 Lausanne, Switzerland
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- Purg, Miha (author)
- Uppsala universitet,Biokemi
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- Saunders, Jake (author)
- Australian Natl Univ, Res Sch Chem, Canberra, ACT 2601, Australia
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- Bauer, Paul (author)
- Uppsala universitet,Biokemi
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- Carr, Paul D. (author)
- Australian Natl Univ, Res Sch Chem, Canberra, ACT 2601, Australia
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- Lin, Ching-Yeh (author)
- Australian Natl Univ, Res Sch Chem, Canberra, ACT 2601, Australia
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- Mabbitt, Peter D. (author)
- Australian Natl Univ, Res Sch Chem, Canberra, ACT 2601, Australia
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- Zhang, William (author)
- Australian Natl Univ, Res Sch Chem, Canberra, ACT 2601, Australia
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- Altamore, Timothy (author)
- Australian Natl Univ, Res Sch Chem, Canberra, ACT 2601, Australia
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- Easton, Chris (author)
- Australian Natl Univ, Res Sch Chem, Canberra, ACT 2601, Australia
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- Coote, Michelle L. (author)
- Australian Natl Univ, Res Sch Chem, Canberra, ACT 2601, Australia
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- Kamerlin, Shina C. Lynn, 1981- (author)
- Uppsala universitet,Biokemi
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- Jackson, Colin J. (author)
- Australian Natl Univ, Res Sch Chem, Canberra, ACT 2601, Australia
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(creator_code:org_t)
- 2018-09-25
- 2018
- English.
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In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9
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Abstract
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- Developments in computational chemistry, bioinformatics, and laboratory evolution have facilitated the de novo design and catalytic optimization of enzymes. Besides creating useful catalysts, the generation and iterative improvement of designed enzymes can provide valuable insight into the interplay between the many phenomena that have been suggested to contribute to catalysis. In this work, we follow changes in conformational sampling, electrostatic preorganization, and quantum tunneling along the evolutionary trajectory of a designed Kemp eliminase. We observe that in the Kemp Eliminase KE07, instability of the designed active site leads to the emergence of two additional active site configurations. Evolutionary conformational selection then gradually stabilizes the most efficient configuration, leading to an improved enzyme. This work exemplifies the link between conformational plasticity and evolvability and demonstrates that residues remote from the active sites of enzymes play crucial roles in controlling and shaping the active site for efficient catalysis.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Hong, Nan-Sook
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Petrovic, Dusan
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Lee, Richmond
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Gryn'ova, Ganna
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Purg, Miha
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Saunders, Jake
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show more...
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Bauer, Paul
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Carr, Paul D.
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Lin, Ching-Yeh
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Mabbitt, Peter D ...
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Zhang, William
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Altamore, Timoth ...
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Easton, Chris
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Coote, Michelle ...
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Kamerlin, Shina ...
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Jackson, Colin J ...
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
- Articles in the publication
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Nature Communica ...
- By the university
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Uppsala University