@misc{10481/86944,
year = {2018},
month = {7},
url = {https://hdl.handle.net/10481/86944},
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. 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},
organization = {Department of Chemistry, BMC, Uppsala University, Box 576, 751 23 Uppsala, Sweden
Departamento de Quimica Fisica, Facultad de Ciencias, University of Granada, 18071 Granada, Spain},
organization = {Wallenberg Academy Fellowship to S.C.L.K. from the Knut and Alice Wallenberg Foundation (KAW 2013.0124)},
organization = {Grant RGP0041/2017 from the Human Frontier Science Program},
organization = {FEDER Funds and grant BIO2015–66426-R to J.M.S.R. from the Spanish Ministry of Economy and Competitiveness},
publisher = {Royal Society},
keywords = {Conformational ensembles},
keywords = {Conformational shifts},
keywords = {De novo enzymes},
title = {Conformational dynamics and enzyme evolution},
doi = {10.1098/rsif.2018.0330},
author = {Petrovic, Dusan and Risso, Valeria Alejandra and Kamerlin, Shina CL and Sánchez Ruiz, José Manuel},
}