Počet záznamů: 1
Coupled Valence-Bond State Molecular Dynamics Description of an Enzyme-Catalyzed Reaction in a Non-Aqueous Organic Solvent
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SYSNO ASEP 0478161 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Coupled Valence-Bond State Molecular Dynamics Description of an Enzyme-Catalyzed Reaction in a Non-Aqueous Organic Solvent Tvůrce(i) Duboué-Dijon, Elise (UOCHB-X) ORCID
Pluhařová, E. (FR)
Domin, D. (FR)
Sen, K. (FR)
Fogarty, A. C. (FR)
Chéron, N. (FR)
Laage, D. (FR)Zdroj.dok. Journal of Physical Chemistry B. - : American Chemical Society - ISSN 1520-6106
Roč. 121, č. 29 (2017), s. 7027-7041Poč.str. 15 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova free energy calculations ; purine nucleoside phosphorylase ; ab initio calculations Vědní obor RIV CF - Fyzikální chemie a teoretická chemie Obor OECD Physical chemistry Institucionální podpora UOCHB-X - RVO:61388963 UT WOS 000406726700005 EID SCOPUS 85026553265 DOI 10.1021/acs.jpcb.7b03102 Anotace Enzymes are widely used in nonaqueous solvents to catalyze non-natural reactions. While experimental measurements showed that the solvent nature has a strong effect on the reaction kinetics, the molecular details of the catalytic mechanism in nonaqueous solvents have remained largely elusive. Here we study the transesterification reaction catalyzed by the paradigm subtilisin Carlsberg serine protease in an organic apolar solvent. The rate-limiting acylation step involves a proton transfer between active-site residues and the nucleophilic attack of the substrate to form a tetrahedral intermediate. We design the first coupled valence-bond state model that simultaneously describes both reactions in the enzymatic active site. We develop a new systematic procedure to parametrize this model on high-level ab initio QM/MM free energy calculations that account for the molecular details of the active site and for both substrate and protein conformational fluctuations. Our calculations show that the reaction energy barrier changes dramatically with the solvent and protein conformational fluctuations. We find that the mechanism of the tetrahedral intermediate formation during the acylation step is similar to that determined under aqueous conditions, and that the proton transfer, and nucleophilic attack reactions occur concertedly. We identify the reaction coordinate to be mostly due to the rearrangement of some residual water molecules close to the active site. Pracoviště Ústav organické chemie a biochemie Kontakt asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Rok sběru 2018
Počet záznamů: 1