Accounting for the instantaneous disorder in the enzyme-substrate Michaelis complex to calculate the Gibbs free energy barrier of an enzyme reaction
Romero Tellez, Sonia (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Cruz Saez, Alejandro (Universitat Autònoma de Barcelona. Departament de Química)
Masgrau, Laura (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
González Lafont, Àngels (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Lluch López, Josep Maria (Universitat Autònoma de Barcelona. Departament de Química)

Date:	2021
Description:	13 pàg.
Abstract:	Many enzyme reactions present instantaneous disorder. These dynamic fluctuations in the enzyme-substrate Michaelis complexes generate a wide range of energy barriers that cannot be experimentally observed, but that determine the measured kinetics of the reaction. These individual energy barriers can be calculated using QM/MM methods, but then the problem is how to deal with this dispersion of energy barriers to provide kinetic information. So far, the most usual procedure has implied the so-called exponential average of the energy barriers. In this paper, we discuss the foundations of this method, and we use the free energy perturbation theory to derive an alternative equation to get the Gibbs free energy barrier of the enzyme reaction. In addition, we propose a practical way to implement it. We have chosen four enzyme reactions as examples. In particular, we have studied the hydrolysis of a glycosidic bond catalyzed by the enzymeThermus thermophilusβ-glycosidase, and the mutant Y284P Ttb-gly, and the hydrogen abstraction reactions from C 13and C 7of arachidonic acid catalyzed by the enzyme rabbit 15-lipoxygenase-1.
Grants:	Agencia Estatal de Investigación CTQ2017-83745-P Ministerio de Ciencia e Innovación PGC2018-098592-B-100
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Language:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Subject:	Acid ; Amber ; Catalytic mechanism ; Conformation ; Lipoxygenases ; Molecular-dynamics simulations ; QM/MM ; Sequence determinants ; Single-molecule ; Specificity
Published in:	Physical chemistry chemical physics, Vol. 23 (June 2021) , p. 13042-13054, ISSN 1463-9084

DOI: 10.1039/d1cp01338f
PMID: 34100037

Postprint 36 p, 1.2 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Articles > Research articles
Articles > Published articles