Conformational dynamics and enzyme evolution
Petrović, Dušan ; Risso, Valeria A ; Kamerlin, Shina Caroline Lynn LU
and Sanchez-Ruiz, Jose M
(2018)
In Journal of the Royal Society, Interface
15(144).
- Abstract
Enzymes are dynamic entities, and their dynamic properties are clearly linked to their biological function. It follows that dynamics ought to play an essential role in enzyme evolution. Indeed, a link between conformational diversity and the emergence of new enzyme functionalities has been recognized for many years. However, it is only recently that state-of-the-art computational and experimental approaches are revealing the crucial molecular details of this link. Specifically, evolutionary trajectories leading to functional optimization for a given host environment or to the emergence of a new function typically involve enriching catalytically competent conformations and/or the freezing out of non-competent conformations of an enzyme.... (More)
Enzymes are dynamic entities, and their dynamic properties are clearly linked to their biological function. It follows that dynamics ought to play an essential role in enzyme evolution. Indeed, a link between conformational diversity and the emergence of new enzyme functionalities has been recognized for many years. However, it is only recently that state-of-the-art computational and experimental approaches are revealing the crucial molecular details of this link. Specifically, evolutionary trajectories leading to functional optimization for a given host environment or to the emergence of a new function typically involve enriching catalytically competent conformations and/or the freezing out of non-competent conformations of an enzyme. In some cases, these evolutionary changes are achieved through distant mutations that shift the protein ensemble towards productive conformations. Multifunctional intermediates in evolutionary trajectories are probably multi-conformational, i.e. able to switch between different overall conformations, each competent for a given function. Conformational diversity can assist the emergence of a completely new active site through a single mutation by facilitating transition-state binding. We propose that this mechanism may have played a role in the emergence of enzymes at the primordial, progenote stage, where it was plausibly promoted by high environmental temperatures and the possibility of additional phenotypic mutations.
(Less)
- author
- Petrović, Dušan
; Risso, Valeria A
; Kamerlin, Shina Caroline Lynn
LU
and Sanchez-Ruiz, Jose M
- publishing date
- 2018-07
- type
- Contribution to journal
- publication status
- published
- keywords
- Catalysis, Catalytic Domain, Enzymes/genetics, Evolution, Molecular, Models, Genetic, Mutation
- in
- Journal of the Royal Society, Interface
- volume
- 15
- issue
- 144
- article number
- 20180330
- publisher
- The Royal Society of Canada
- external identifiers
-
- scopus:85051432104
- pmid:30021929
- ISSN
- 1742-5662
- DOI
- 10.1098/rsif.2018.0330
- language
- English
- LU publication?
- no
- additional info
- © 2018 The Author(s).
- id
- 607a2b66-4f6e-4adc-8832-0d8ef7e59521
- date added to LUP
- 2025-01-11 21:04:24
- date last changed
- 2025-07-28 09:34:16
@article{607a2b66-4f6e-4adc-8832-0d8ef7e59521,
abstract = {{<p>Enzymes are dynamic entities, and their dynamic properties are clearly linked to their biological function. It follows that dynamics ought to play an essential role in enzyme evolution. Indeed, a link between conformational diversity and the emergence of new enzyme functionalities has been recognized for many years. However, it is only recently that state-of-the-art computational and experimental approaches are revealing the crucial molecular details of this link. Specifically, evolutionary trajectories leading to functional optimization for a given host environment or to the emergence of a new function typically involve enriching catalytically competent conformations and/or the freezing out of non-competent conformations of an enzyme. In some cases, these evolutionary changes are achieved through distant mutations that shift the protein ensemble towards productive conformations. Multifunctional intermediates in evolutionary trajectories are probably multi-conformational, i.e. able to switch between different overall conformations, each competent for a given function. Conformational diversity can assist the emergence of a completely new active site through a single mutation by facilitating transition-state binding. We propose that this mechanism may have played a role in the emergence of enzymes at the primordial, progenote stage, where it was plausibly promoted by high environmental temperatures and the possibility of additional phenotypic mutations.</p>}},
author = {{Petrović, Dušan and Risso, Valeria A and Kamerlin, Shina Caroline Lynn and Sanchez-Ruiz, Jose M}},
issn = {{1742-5662}},
keywords = {{Catalysis; Catalytic Domain; Enzymes/genetics; Evolution, Molecular; Models, Genetic; Mutation}},
language = {{eng}},
number = {{144}},
publisher = {{The Royal Society of Canada}},
series = {{Journal of the Royal Society, Interface}},
title = {{Conformational dynamics and enzyme evolution}},
url = {{http://dx.doi.org/10.1098/rsif.2018.0330}},
doi = {{10.1098/rsif.2018.0330}},
volume = {{15}},
year = {{2018}},
}