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Path Integral Calculation of the Hydrogen/Deuterium Kinetic Isotope Effect in Monoamine Oxidase A-Catalyzed Decomposition of Benzylamine
Monoamine oxidase A (MAO A) is a well-known enzyme responsible for the oxidative deamination of several important monoaminergic neurotransmitters. The rate-limiting step of amine decomposition is hydride anion transfer from the substrate α–CH2 group to the N5 atom of the flavin cofactor moiety. In t...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930584/ https://www.ncbi.nlm.nih.gov/pubmed/31795294 http://dx.doi.org/10.3390/molecules24234359 |
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author | Brela, Mateusz Z. Prah, Alja Boczar, Marek Stare, Jernej Mavri, Janez |
author_facet | Brela, Mateusz Z. Prah, Alja Boczar, Marek Stare, Jernej Mavri, Janez |
author_sort | Brela, Mateusz Z. |
collection | PubMed |
description | Monoamine oxidase A (MAO A) is a well-known enzyme responsible for the oxidative deamination of several important monoaminergic neurotransmitters. The rate-limiting step of amine decomposition is hydride anion transfer from the substrate α–CH2 group to the N5 atom of the flavin cofactor moiety. In this work, we focus on MAO A-catalyzed benzylamine decomposition in order to elucidate nuclear quantum effects through the calculation of the hydrogen/deuterium (H/D) kinetic isotope effect. The rate-limiting step of the reaction was simulated using a multiscale approach at the empirical valence bond (EVB) level. We applied path integral quantization using the quantum classical path method (QCP) for the substrate benzylamine as well as the MAO cofactor flavin adenine dinucleotide. The calculated H/D kinetic isotope effect of 6.5 ± 1.4 is in reasonable agreement with the available experimental values. |
format | Online Article Text |
id | pubmed-6930584 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-69305842019-12-26 Path Integral Calculation of the Hydrogen/Deuterium Kinetic Isotope Effect in Monoamine Oxidase A-Catalyzed Decomposition of Benzylamine Brela, Mateusz Z. Prah, Alja Boczar, Marek Stare, Jernej Mavri, Janez Molecules Article Monoamine oxidase A (MAO A) is a well-known enzyme responsible for the oxidative deamination of several important monoaminergic neurotransmitters. The rate-limiting step of amine decomposition is hydride anion transfer from the substrate α–CH2 group to the N5 atom of the flavin cofactor moiety. In this work, we focus on MAO A-catalyzed benzylamine decomposition in order to elucidate nuclear quantum effects through the calculation of the hydrogen/deuterium (H/D) kinetic isotope effect. The rate-limiting step of the reaction was simulated using a multiscale approach at the empirical valence bond (EVB) level. We applied path integral quantization using the quantum classical path method (QCP) for the substrate benzylamine as well as the MAO cofactor flavin adenine dinucleotide. The calculated H/D kinetic isotope effect of 6.5 ± 1.4 is in reasonable agreement with the available experimental values. MDPI 2019-11-28 /pmc/articles/PMC6930584/ /pubmed/31795294 http://dx.doi.org/10.3390/molecules24234359 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Brela, Mateusz Z. Prah, Alja Boczar, Marek Stare, Jernej Mavri, Janez Path Integral Calculation of the Hydrogen/Deuterium Kinetic Isotope Effect in Monoamine Oxidase A-Catalyzed Decomposition of Benzylamine |
title | Path Integral Calculation of the Hydrogen/Deuterium Kinetic Isotope Effect in Monoamine Oxidase A-Catalyzed Decomposition of Benzylamine |
title_full | Path Integral Calculation of the Hydrogen/Deuterium Kinetic Isotope Effect in Monoamine Oxidase A-Catalyzed Decomposition of Benzylamine |
title_fullStr | Path Integral Calculation of the Hydrogen/Deuterium Kinetic Isotope Effect in Monoamine Oxidase A-Catalyzed Decomposition of Benzylamine |
title_full_unstemmed | Path Integral Calculation of the Hydrogen/Deuterium Kinetic Isotope Effect in Monoamine Oxidase A-Catalyzed Decomposition of Benzylamine |
title_short | Path Integral Calculation of the Hydrogen/Deuterium Kinetic Isotope Effect in Monoamine Oxidase A-Catalyzed Decomposition of Benzylamine |
title_sort | path integral calculation of the hydrogen/deuterium kinetic isotope effect in monoamine oxidase a-catalyzed decomposition of benzylamine |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930584/ https://www.ncbi.nlm.nih.gov/pubmed/31795294 http://dx.doi.org/10.3390/molecules24234359 |
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