Loop dynamics and the evolution of enzyme activity
Corbella, Marina ; Pinto, Gaspar P and Kamerlin, Shina C L LU
(2023)
In Nature reviews. Chemistry
7(8).
p.536-547
- Abstract
In the early 2000s, Tawfik presented his 'New View' on enzyme evolution, highlighting the role of conformational plasticity in expanding the functional diversity of limited repertoires of sequences. This view is gaining increasing traction with increasing evidence of the importance of conformational dynamics in both natural and laboratory evolution of enzymes. The past years have seen several elegant examples of harnessing conformational (particularly loop) dynamics to successfully manipulate protein function. This Review revisits flexible loops as critical participants in regulating enzyme activity. We showcase several systems of particular interest: triosephosphate isomerase barrel proteins, protein tyrosine phosphatases and... (More)
In the early 2000s, Tawfik presented his 'New View' on enzyme evolution, highlighting the role of conformational plasticity in expanding the functional diversity of limited repertoires of sequences. This view is gaining increasing traction with increasing evidence of the importance of conformational dynamics in both natural and laboratory evolution of enzymes. The past years have seen several elegant examples of harnessing conformational (particularly loop) dynamics to successfully manipulate protein function. This Review revisits flexible loops as critical participants in regulating enzyme activity. We showcase several systems of particular interest: triosephosphate isomerase barrel proteins, protein tyrosine phosphatases and β-lactamases, while briefly discussing other systems in which loop dynamics are important for selectivity and turnover. We then discuss the implications for engineering, presenting examples of successful loop manipulation in either improving catalytic efficiency, or changing selectivity completely. Overall, it is becoming clearer that mimicking nature by manipulating the conformational dynamics of key protein loops is a powerful method of tailoring enzyme activity, without needing to target active-site residues.
(Less)
- author
- Corbella, Marina
; Pinto, Gaspar P
and Kamerlin, Shina C L
LU
- publishing date
- 2023-08
- type
- Contribution to journal
- publication status
- published
- keywords
- Humans, Triose-Phosphate Isomerase/genetics, Catalysis
- in
- Nature reviews. Chemistry
- volume
- 7
- issue
- 8
- pages
- 12 pages
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:37225920
- scopus:85160222454
- ISSN
- 2397-3358
- DOI
- 10.1038/s41570-023-00495-w
- language
- English
- LU publication?
- no
- additional info
- © 2023. Springer Nature Limited.
- id
- a0c317cb-840c-4e29-801a-90a6f7a8118e
- date added to LUP
- 2025-01-11 18:41:08
- date last changed
- 2025-07-14 07:52:05
@article{a0c317cb-840c-4e29-801a-90a6f7a8118e,
abstract = {{<p>In the early 2000s, Tawfik presented his 'New View' on enzyme evolution, highlighting the role of conformational plasticity in expanding the functional diversity of limited repertoires of sequences. This view is gaining increasing traction with increasing evidence of the importance of conformational dynamics in both natural and laboratory evolution of enzymes. The past years have seen several elegant examples of harnessing conformational (particularly loop) dynamics to successfully manipulate protein function. This Review revisits flexible loops as critical participants in regulating enzyme activity. We showcase several systems of particular interest: triosephosphate isomerase barrel proteins, protein tyrosine phosphatases and β-lactamases, while briefly discussing other systems in which loop dynamics are important for selectivity and turnover. We then discuss the implications for engineering, presenting examples of successful loop manipulation in either improving catalytic efficiency, or changing selectivity completely. Overall, it is becoming clearer that mimicking nature by manipulating the conformational dynamics of key protein loops is a powerful method of tailoring enzyme activity, without needing to target active-site residues.</p>}},
author = {{Corbella, Marina and Pinto, Gaspar P and Kamerlin, Shina C L}},
issn = {{2397-3358}},
keywords = {{Humans; Triose-Phosphate Isomerase/genetics; Catalysis}},
language = {{eng}},
number = {{8}},
pages = {{536--547}},
publisher = {{Nature Publishing Group}},
series = {{Nature reviews. Chemistry}},
title = {{Loop dynamics and the evolution of enzyme activity}},
url = {{http://dx.doi.org/10.1038/s41570-023-00495-w}},
doi = {{10.1038/s41570-023-00495-w}},
volume = {{7}},
year = {{2023}},
}