The evolution of multiple active site configurations in a designed enzyme

Nan-Sook Hong, Dušan Petrović, Richmond Lee, Ganna Gryn’ova, Miha Purg, Jake Saunders, Paul Bauer, Paul D. Carr, Ching-Yeh Lin, Peter D. Mabbitt, William Zhang, Timothy Altamore, Chris Easton, Michelle L. Coote, Shina C. L. Kamerlin () and Colin J. Jackson ()
Additional contact information
Nan-Sook Hong: Australian National University
Dušan Petrović: Uppsala University
Richmond Lee: Australian National University
Ganna Gryn’ova: Australian National University
Miha Purg: Uppsala University
Jake Saunders: Australian National University
Paul Bauer: Uppsala University
Paul D. Carr: Australian National University
Ching-Yeh Lin: Australian National University
Peter D. Mabbitt: Australian National University
William Zhang: Australian National University
Timothy Altamore: Australian National University
Chris Easton: Australian National University
Michelle L. Coote: Australian National University
Shina C. L. Kamerlin: Uppsala University
Colin J. Jackson: Australian National University

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: Abstract 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.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-06305-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06305-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-06305-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().