Molecular rules for selectivity in lipase-catalysed acylation of lysine
The selectivity of L-lysine acylation by lauric acid catalysed by Candida antarctica lipase B (CALB) was investigated combining experimental and theoretical methodologies. Experiments showed the near-exclusive acylation of lysine $ε$-amino group; only traces of product resulting from the acylation o...
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ftdatacite:10.48550/arxiv.1905.08518 2023-05-15T13:59:09+02:00 Molecular rules for selectivity in lipase-catalysed acylation of lysine Dettori, L. Jelsch, Christian Guiavarc'h, Y. Delaunay, S. Framboisier, X. Chevalot, I. Humeau, C. 2019 https://dx.doi.org/10.48550/arxiv.1905.08518 https://arxiv.org/abs/1905.08518 unknown arXiv https://dx.doi.org/10.1016/j.procbio.2018.07.021 arXiv.org perpetual, non-exclusive license http://arxiv.org/licenses/nonexclusive-distrib/1.0/ Quantitative Methods q-bio.QM Chemical Physics physics.chem-ph Biomolecules q-bio.BM FOS Biological sciences FOS Physical sciences article-journal Article ScholarlyArticle Text 2019 ftdatacite https://doi.org/10.48550/arxiv.1905.08518 https://doi.org/10.1016/j.procbio.2018.07.021 2022-04-01T08:38:23Z The selectivity of L-lysine acylation by lauric acid catalysed by Candida antarctica lipase B (CALB) was investigated combining experimental and theoretical methodologies. Experiments showed the near-exclusive acylation of lysine $ε$-amino group; only traces of product resulting from the acylation of lysine $α$-amino group were observed fleetingly. Molecular modelling simulations were performed aiming to understand the molecular rules for selectivity. Flexible docking simulations combined with structural investigations into lysine/CALB binding modes also suggested the preferential acylation of lysine $ε$-amino group without, however, excluding the acylation of the lysine $α$-amino group. Electrostatic interaction energy between lysine and the residues covering the catalytic cavity was calculated in order to understand the discrimination between the two lysine amino groups. The results suggests that the proximity of the carboxylate group hinders the binding of the substrate in configurations enabling the N$α$-acylation. Key interactions with the polar region covering the catalytic triad were identified and a plausible explanation for selectivity was proposed. Text Antarc* Antarctica DataCite Metadata Store (German National Library of Science and Technology) |
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Quantitative Methods q-bio.QM Chemical Physics physics.chem-ph Biomolecules q-bio.BM FOS Biological sciences FOS Physical sciences |
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Quantitative Methods q-bio.QM Chemical Physics physics.chem-ph Biomolecules q-bio.BM FOS Biological sciences FOS Physical sciences Dettori, L. Jelsch, Christian Guiavarc'h, Y. Delaunay, S. Framboisier, X. Chevalot, I. Humeau, C. Molecular rules for selectivity in lipase-catalysed acylation of lysine |
topic_facet |
Quantitative Methods q-bio.QM Chemical Physics physics.chem-ph Biomolecules q-bio.BM FOS Biological sciences FOS Physical sciences |
description |
The selectivity of L-lysine acylation by lauric acid catalysed by Candida antarctica lipase B (CALB) was investigated combining experimental and theoretical methodologies. Experiments showed the near-exclusive acylation of lysine $ε$-amino group; only traces of product resulting from the acylation of lysine $α$-amino group were observed fleetingly. Molecular modelling simulations were performed aiming to understand the molecular rules for selectivity. Flexible docking simulations combined with structural investigations into lysine/CALB binding modes also suggested the preferential acylation of lysine $ε$-amino group without, however, excluding the acylation of the lysine $α$-amino group. Electrostatic interaction energy between lysine and the residues covering the catalytic cavity was calculated in order to understand the discrimination between the two lysine amino groups. The results suggests that the proximity of the carboxylate group hinders the binding of the substrate in configurations enabling the N$α$-acylation. Key interactions with the polar region covering the catalytic triad were identified and a plausible explanation for selectivity was proposed. |
format |
Text |
author |
Dettori, L. Jelsch, Christian Guiavarc'h, Y. Delaunay, S. Framboisier, X. Chevalot, I. Humeau, C. |
author_facet |
Dettori, L. Jelsch, Christian Guiavarc'h, Y. Delaunay, S. Framboisier, X. Chevalot, I. Humeau, C. |
author_sort |
Dettori, L. |
title |
Molecular rules for selectivity in lipase-catalysed acylation of lysine |
title_short |
Molecular rules for selectivity in lipase-catalysed acylation of lysine |
title_full |
Molecular rules for selectivity in lipase-catalysed acylation of lysine |
title_fullStr |
Molecular rules for selectivity in lipase-catalysed acylation of lysine |
title_full_unstemmed |
Molecular rules for selectivity in lipase-catalysed acylation of lysine |
title_sort |
molecular rules for selectivity in lipase-catalysed acylation of lysine |
publisher |
arXiv |
publishDate |
2019 |
url |
https://dx.doi.org/10.48550/arxiv.1905.08518 https://arxiv.org/abs/1905.08518 |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_relation |
https://dx.doi.org/10.1016/j.procbio.2018.07.021 |
op_rights |
arXiv.org perpetual, non-exclusive license http://arxiv.org/licenses/nonexclusive-distrib/1.0/ |
op_doi |
https://doi.org/10.48550/arxiv.1905.08518 https://doi.org/10.1016/j.procbio.2018.07.021 |
_version_ |
1766267599325233152 |