Molecular Modeling of Quercetin Acetylation by Lipases: Study of Enzyme-Substrate Interactions
Accès restreint aux membres de l'Université de Lorraine jusqu'au 2015-12-01 Quercetin (QCT) is a plant-produced polyphenolic compound well-known for its antioxidant activities and beneficial health effects. Its solubility, stability, bioavailability and biological activities may be improve...
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2012
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ftunilorrainehal:oai:HAL:tel-01749457v1 2023-10-25T01:29:35+02:00 Molecular Modeling of Quercetin Acetylation by Lipases: Study of Enzyme-Substrate Interactions Modélisation moléculaire de l'acétylation de la quercétine par des lipases : étude des interactions enzyme-substrat Bidouil, Christelle Laboratoire d'Ingénierie des Biomolécules (LIBio) Université de Lorraine (UL) Université de Lorraine Jean-Marc Engasser Catherine Humeau-Virot 2012-11-13 https://hal.univ-lorraine.fr/tel-01749457 https://hal.univ-lorraine.fr/tel-01749457/document https://hal.univ-lorraine.fr/tel-01749457/file/DDOC_T_2012_0263_BIDOUIL.pdf fr fre HAL CCSD NNT: 2012LORR0263 tel-01749457 https://hal.univ-lorraine.fr/tel-01749457 https://hal.univ-lorraine.fr/tel-01749457/document https://hal.univ-lorraine.fr/tel-01749457/file/DDOC_T_2012_0263_BIDOUIL.pdf info:eu-repo/semantics/OpenAccess https://hal.univ-lorraine.fr/tel-01749457 Alimentation et Nutrition. Université de Lorraine, 2012. Français. ⟨NNT : 2012LORR0263⟩ Quercetin Candida antarctica Lipase B (CALB) Acetylation Molecular modeling Docking Molecular Dynamics Quercétine Lipase B de Candida antarctica Modélisation moléculaire Dynamique moléculaire Flavonoïdes Lipases [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition info:eu-repo/semantics/doctoralThesis Theses 2012 ftunilorrainehal 2023-09-26T23:01:24Z Accès restreint aux membres de l'Université de Lorraine jusqu'au 2015-12-01 Quercetin (QCT) is a plant-produced polyphenolic compound well-known for its antioxidant activities and beneficial health effects. Its solubility, stability, bioavailability and biological activities may be improved by a selective acylation of its hydroxyl groups. This work aims at studying the possibility of QCT enzymatic acetylation by Candida antarctica lipase B (CALB), the most industrially exploited lipase for regio- and enantioselective esterifications. In prospect of the rational enzyme design, a molecular modeling approach was implemented to understand the interactions that govern the substrate positioning and orientation in the lipase's active site. In a first experimental part, the absence of CALB acetylation activity towards quercetin in excess of vinyl acetate was confirmed. In a second part, this inactivity of CALB was explained by means of docking and molecular dynamics simulations. This results from an inappropriate positioning of the acyl donor linked to the catalytic serine and from an insufficient proximity of QCT hydroxyls vis-à-vis catalytic residues. The distance of QCT from the catalytic triad is due to its rigidity and to the narrow active site as well as to hydrophobic and electrostatic interactions between the substrate and the cavity residues. On the contrary, this molecular simulation approach predicts an appropriate positioning of both substrates in the active site of Pseudomonas cepacia lipase (PCL), which can perform QCT acetylation. In a third part, the impact of mutations of two residues implicated in the stabilization of QCT by hydrophobic interactions in CALB was investigated through simulations. The substitution of isoleucines by alanines and valines led to an increase in the catalytic pocket volume which intensified the mobility of QCT. However, these mutations are insufficient to allow an appropriate positioning of acetate and QCT in relation to the catalytic triad. The last part of this work ... Doctoral or Postdoctoral Thesis Antarc* Antarctica Université de Lorraine: HAL |
institution |
Open Polar |
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Université de Lorraine: HAL |
op_collection_id |
ftunilorrainehal |
language |
French |
topic |
Quercetin Candida antarctica Lipase B (CALB) Acetylation Molecular modeling Docking Molecular Dynamics Quercétine Lipase B de Candida antarctica Modélisation moléculaire Dynamique moléculaire Flavonoïdes Lipases [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition |
spellingShingle |
Quercetin Candida antarctica Lipase B (CALB) Acetylation Molecular modeling Docking Molecular Dynamics Quercétine Lipase B de Candida antarctica Modélisation moléculaire Dynamique moléculaire Flavonoïdes Lipases [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition Bidouil, Christelle Molecular Modeling of Quercetin Acetylation by Lipases: Study of Enzyme-Substrate Interactions |
topic_facet |
Quercetin Candida antarctica Lipase B (CALB) Acetylation Molecular modeling Docking Molecular Dynamics Quercétine Lipase B de Candida antarctica Modélisation moléculaire Dynamique moléculaire Flavonoïdes Lipases [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition |
description |
Accès restreint aux membres de l'Université de Lorraine jusqu'au 2015-12-01 Quercetin (QCT) is a plant-produced polyphenolic compound well-known for its antioxidant activities and beneficial health effects. Its solubility, stability, bioavailability and biological activities may be improved by a selective acylation of its hydroxyl groups. This work aims at studying the possibility of QCT enzymatic acetylation by Candida antarctica lipase B (CALB), the most industrially exploited lipase for regio- and enantioselective esterifications. In prospect of the rational enzyme design, a molecular modeling approach was implemented to understand the interactions that govern the substrate positioning and orientation in the lipase's active site. In a first experimental part, the absence of CALB acetylation activity towards quercetin in excess of vinyl acetate was confirmed. In a second part, this inactivity of CALB was explained by means of docking and molecular dynamics simulations. This results from an inappropriate positioning of the acyl donor linked to the catalytic serine and from an insufficient proximity of QCT hydroxyls vis-à-vis catalytic residues. The distance of QCT from the catalytic triad is due to its rigidity and to the narrow active site as well as to hydrophobic and electrostatic interactions between the substrate and the cavity residues. On the contrary, this molecular simulation approach predicts an appropriate positioning of both substrates in the active site of Pseudomonas cepacia lipase (PCL), which can perform QCT acetylation. In a third part, the impact of mutations of two residues implicated in the stabilization of QCT by hydrophobic interactions in CALB was investigated through simulations. The substitution of isoleucines by alanines and valines led to an increase in the catalytic pocket volume which intensified the mobility of QCT. However, these mutations are insufficient to allow an appropriate positioning of acetate and QCT in relation to the catalytic triad. The last part of this work ... |
author2 |
Laboratoire d'Ingénierie des Biomolécules (LIBio) Université de Lorraine (UL) Université de Lorraine Jean-Marc Engasser Catherine Humeau-Virot |
format |
Doctoral or Postdoctoral Thesis |
author |
Bidouil, Christelle |
author_facet |
Bidouil, Christelle |
author_sort |
Bidouil, Christelle |
title |
Molecular Modeling of Quercetin Acetylation by Lipases: Study of Enzyme-Substrate Interactions |
title_short |
Molecular Modeling of Quercetin Acetylation by Lipases: Study of Enzyme-Substrate Interactions |
title_full |
Molecular Modeling of Quercetin Acetylation by Lipases: Study of Enzyme-Substrate Interactions |
title_fullStr |
Molecular Modeling of Quercetin Acetylation by Lipases: Study of Enzyme-Substrate Interactions |
title_full_unstemmed |
Molecular Modeling of Quercetin Acetylation by Lipases: Study of Enzyme-Substrate Interactions |
title_sort |
molecular modeling of quercetin acetylation by lipases: study of enzyme-substrate interactions |
publisher |
HAL CCSD |
publishDate |
2012 |
url |
https://hal.univ-lorraine.fr/tel-01749457 https://hal.univ-lorraine.fr/tel-01749457/document https://hal.univ-lorraine.fr/tel-01749457/file/DDOC_T_2012_0263_BIDOUIL.pdf |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_source |
https://hal.univ-lorraine.fr/tel-01749457 Alimentation et Nutrition. Université de Lorraine, 2012. Français. ⟨NNT : 2012LORR0263⟩ |
op_relation |
NNT: 2012LORR0263 tel-01749457 https://hal.univ-lorraine.fr/tel-01749457 https://hal.univ-lorraine.fr/tel-01749457/document https://hal.univ-lorraine.fr/tel-01749457/file/DDOC_T_2012_0263_BIDOUIL.pdf |
op_rights |
info:eu-repo/semantics/OpenAccess |
_version_ |
1780733463147577344 |