Impact of Sucrose as Osmolyte on Molecular Dynamics of Mouse Acetylcholinesterase
The enzyme model, mouse acetylcholinesterase, which exhibits its active site at the bottom of a narrow gorge, was investigated in the presence of different concentrations of sucrose to shed light on the protein and water dynamics in cholinesterases. The study was conducted by incoherent neutron scat...
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MDPI AG
2020-12-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/12/1664 |
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| author | Sofya V. Lushchekina Gaetan Inidjel Nicolas Martinez Patrick Masson Marie Trovaslet-Leroy Florian Nachon Michael Marek Koza Tilo Seydel Judith Peters |
| author_facet | Sofya V. Lushchekina Gaetan Inidjel Nicolas Martinez Patrick Masson Marie Trovaslet-Leroy Florian Nachon Michael Marek Koza Tilo Seydel Judith Peters |
| author_sort | Sofya V. Lushchekina |
| collection | DOAJ |
| description | The enzyme model, mouse acetylcholinesterase, which exhibits its active site at the bottom of a narrow gorge, was investigated in the presence of different concentrations of sucrose to shed light on the protein and water dynamics in cholinesterases. The study was conducted by incoherent neutron scattering, giving access to molecular dynamics within the time scale of sub-nano to nanoseconds, in comparison with molecular dynamics simulations. With increasing sucrose concentration, we found non-linear effects, e.g., first a decrease in the dynamics at 5 wt% followed by a gain at 10 wt% sucrose. Direct comparisons with simulations permitted us to understand the following findings: at 5 wt%, sugar molecules interact with the protein surface through water molecules and damp the motions to reduce the overall protein mobility, although the motions inside the gorge are enhanced due to water depletion. When going to 10 wt% of sucrose, some water molecules at the protein surface are replaced by sugar molecules. By penetrating the protein surface, they disrupt some of the intra-protein contacts, and induce new ones, creating new pathways for correlated motions, and therefore, increasing the dynamics. This exhaustive study allowed for an explanation of the detail interactions leading to the observed non-linear behavior. |
| first_indexed | 2024-03-10T14:08:03Z |
| format | Article |
| id | doaj.art-b4e57c4c55a346208e146917c7f97629 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T14:08:03Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-b4e57c4c55a346208e146917c7f976292023-11-21T00:31:24ZengMDPI AGBiomolecules2218-273X2020-12-011012166410.3390/biom10121664Impact of Sucrose as Osmolyte on Molecular Dynamics of Mouse AcetylcholinesteraseSofya V. Lushchekina0Gaetan Inidjel1Nicolas Martinez2Patrick Masson3Marie Trovaslet-Leroy4Florian Nachon5Michael Marek Koza6Tilo Seydel7Judith Peters8N.M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 119334 Moscow, RussiaInstitut Laue Langevin, 38000 Grenoble, FranceInstitut Laue Langevin, 38000 Grenoble, FranceNeuropharmacology Laboratory, Kazan Federal University, Kremlevskaya str 18, 480002 Kazan, RussiaInstitut de Recherche Biomédicale des Armées, 91223 Brétigny sur Orge, FranceInstitut de Recherche Biomédicale des Armées, 91223 Brétigny sur Orge, FranceInstitut Laue Langevin, 38000 Grenoble, FranceInstitut Laue Langevin, 38000 Grenoble, FranceInstitut Laue Langevin, 38000 Grenoble, FranceThe enzyme model, mouse acetylcholinesterase, which exhibits its active site at the bottom of a narrow gorge, was investigated in the presence of different concentrations of sucrose to shed light on the protein and water dynamics in cholinesterases. The study was conducted by incoherent neutron scattering, giving access to molecular dynamics within the time scale of sub-nano to nanoseconds, in comparison with molecular dynamics simulations. With increasing sucrose concentration, we found non-linear effects, e.g., first a decrease in the dynamics at 5 wt% followed by a gain at 10 wt% sucrose. Direct comparisons with simulations permitted us to understand the following findings: at 5 wt%, sugar molecules interact with the protein surface through water molecules and damp the motions to reduce the overall protein mobility, although the motions inside the gorge are enhanced due to water depletion. When going to 10 wt% of sucrose, some water molecules at the protein surface are replaced by sugar molecules. By penetrating the protein surface, they disrupt some of the intra-protein contacts, and induce new ones, creating new pathways for correlated motions, and therefore, increasing the dynamics. This exhaustive study allowed for an explanation of the detail interactions leading to the observed non-linear behavior.https://www.mdpi.com/2218-273X/10/12/1664cholinesteraseosmotic stressneutron scatteringmolecular dynamicsMD simulations |
| spellingShingle | Sofya V. Lushchekina Gaetan Inidjel Nicolas Martinez Patrick Masson Marie Trovaslet-Leroy Florian Nachon Michael Marek Koza Tilo Seydel Judith Peters Impact of Sucrose as Osmolyte on Molecular Dynamics of Mouse Acetylcholinesterase Biomolecules cholinesterase osmotic stress neutron scattering molecular dynamics MD simulations |
| title | Impact of Sucrose as Osmolyte on Molecular Dynamics of Mouse Acetylcholinesterase |
| title_full | Impact of Sucrose as Osmolyte on Molecular Dynamics of Mouse Acetylcholinesterase |
| title_fullStr | Impact of Sucrose as Osmolyte on Molecular Dynamics of Mouse Acetylcholinesterase |
| title_full_unstemmed | Impact of Sucrose as Osmolyte on Molecular Dynamics of Mouse Acetylcholinesterase |
| title_short | Impact of Sucrose as Osmolyte on Molecular Dynamics of Mouse Acetylcholinesterase |
| title_sort | impact of sucrose as osmolyte on molecular dynamics of mouse acetylcholinesterase |
| topic | cholinesterase osmotic stress neutron scattering molecular dynamics MD simulations |
| url | https://www.mdpi.com/2218-273X/10/12/1664 |
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