A Correlation between the Activity of Candida antarctica Lipase B and Differences in Binding Free Energies of Organic Solvent and Substrate
The ability of enzymes to operate in organic solvent is now widely accepted and is the basis for extensive research in enzymology. The challenge is to select the solvent media that allows the modulation of enzyme activity. For a rational selection of a solvent, it is necessary to understand the effe...
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ftdtupubl:oai:pure.atira.dk:publications/2d9ab8bd-5120-4882-85b9-2febd4f69b81 2024-09-15T17:42:04+00:00 A Correlation between the Activity of Candida antarctica Lipase B and Differences in Binding Free Energies of Organic Solvent and Substrate Banik, Sindrila Dutta Nordblad, Mathias Woodley, John Peters, Günther H.J. 2016 https://orbit.dtu.dk/en/publications/2d9ab8bd-5120-4882-85b9-2febd4f69b81 https://doi.org/10.1021/acscatal.6b02073 eng eng https://orbit.dtu.dk/en/publications/2d9ab8bd-5120-4882-85b9-2febd4f69b81 info:eu-repo/semantics/closedAccess Banik , S D , Nordblad , M , Woodley , J & Peters , G H J 2016 , ' A Correlation between the Activity of Candida antarctica Lipase B and Differences in Binding Free Energies of Organic Solvent and Substrate ' , ACS Catalysis , vol. 6 , no. 10 , pp. 6350-6361 . https://doi.org/10.1021/acscatal.6b02073 SPECIFICITY Lipase B Candida antarctica lipase B Binding free energies article 2016 ftdtupubl https://doi.org/10.1021/acscatal.6b02073 2024-08-05T23:48:29Z The ability of enzymes to operate in organic solvent is now widely accepted and is the basis for extensive research in enzymology. The challenge is to select the solvent media that allows the modulation of enzyme activity. For a rational selection of a solvent, it is necessary to understand the effect of organic solvent molecules on enzyme structure and the enzymatic reaction on a molecular level. To gain such insight, we combined experimental kinetics studies with full atomic molecular dynamics simulations and found a correlation between the activity of Candida antarctica lipase B (CALB) [for the esterification reaction between butyric acid and ethanol at a fixed water activity] and the binding of the solvent/substrate molecules in the active site region of CALB. We have investigated the influence of four organic solvents hexane (HEX), methyl tertiary butyl ether (MTBE), acetonitrile (ACN), and tertiary butanol (TBU)-on the catalytic activity of CALB for the esterification reaction. The solvents have been chosen on the basis of different polarity/functional groups. Our study shows that these organic solvents do not alter the overall conformation of CALB; rather, the solvent effects on the performance of the enzyme may be ascribed to binding of solvent molecules to the enzyme active site region and the solvation energy of substrate molecules in the different solvents. Polar solvent molecules interact strongly with CALB and compete with the substrate to bind to the active site region, resulting in an inhibitory effect which is also confirmed by the binding free energies for the solvent and substrate molecules estimated from the simulations. Consequently, the catalytic activity of CALB decreases in polar solvents. This effect is significant, and CALB is over 10 orders of magnitude more active in nonpolar solvents (HEX and MTBE) than in the polar solvents (ACN and TBU). TBU molecules show an exceptional behavior because the solvent molecule forms an extensive hydrogen bond network within the CALB active site region ... Article in Journal/Newspaper Antarc* Antarctica Technical University of Denmark: DTU Orbit ACS Catalysis 6 10 6350 6361 |
institution |
Open Polar |
collection |
Technical University of Denmark: DTU Orbit |
op_collection_id |
ftdtupubl |
language |
English |
topic |
SPECIFICITY Lipase B Candida antarctica lipase B Binding free energies |
spellingShingle |
SPECIFICITY Lipase B Candida antarctica lipase B Binding free energies Banik, Sindrila Dutta Nordblad, Mathias Woodley, John Peters, Günther H.J. A Correlation between the Activity of Candida antarctica Lipase B and Differences in Binding Free Energies of Organic Solvent and Substrate |
topic_facet |
SPECIFICITY Lipase B Candida antarctica lipase B Binding free energies |
description |
The ability of enzymes to operate in organic solvent is now widely accepted and is the basis for extensive research in enzymology. The challenge is to select the solvent media that allows the modulation of enzyme activity. For a rational selection of a solvent, it is necessary to understand the effect of organic solvent molecules on enzyme structure and the enzymatic reaction on a molecular level. To gain such insight, we combined experimental kinetics studies with full atomic molecular dynamics simulations and found a correlation between the activity of Candida antarctica lipase B (CALB) [for the esterification reaction between butyric acid and ethanol at a fixed water activity] and the binding of the solvent/substrate molecules in the active site region of CALB. We have investigated the influence of four organic solvents hexane (HEX), methyl tertiary butyl ether (MTBE), acetonitrile (ACN), and tertiary butanol (TBU)-on the catalytic activity of CALB for the esterification reaction. The solvents have been chosen on the basis of different polarity/functional groups. Our study shows that these organic solvents do not alter the overall conformation of CALB; rather, the solvent effects on the performance of the enzyme may be ascribed to binding of solvent molecules to the enzyme active site region and the solvation energy of substrate molecules in the different solvents. Polar solvent molecules interact strongly with CALB and compete with the substrate to bind to the active site region, resulting in an inhibitory effect which is also confirmed by the binding free energies for the solvent and substrate molecules estimated from the simulations. Consequently, the catalytic activity of CALB decreases in polar solvents. This effect is significant, and CALB is over 10 orders of magnitude more active in nonpolar solvents (HEX and MTBE) than in the polar solvents (ACN and TBU). TBU molecules show an exceptional behavior because the solvent molecule forms an extensive hydrogen bond network within the CALB active site region ... |
format |
Article in Journal/Newspaper |
author |
Banik, Sindrila Dutta Nordblad, Mathias Woodley, John Peters, Günther H.J. |
author_facet |
Banik, Sindrila Dutta Nordblad, Mathias Woodley, John Peters, Günther H.J. |
author_sort |
Banik, Sindrila Dutta |
title |
A Correlation between the Activity of Candida antarctica Lipase B and Differences in Binding Free Energies of Organic Solvent and Substrate |
title_short |
A Correlation between the Activity of Candida antarctica Lipase B and Differences in Binding Free Energies of Organic Solvent and Substrate |
title_full |
A Correlation between the Activity of Candida antarctica Lipase B and Differences in Binding Free Energies of Organic Solvent and Substrate |
title_fullStr |
A Correlation between the Activity of Candida antarctica Lipase B and Differences in Binding Free Energies of Organic Solvent and Substrate |
title_full_unstemmed |
A Correlation between the Activity of Candida antarctica Lipase B and Differences in Binding Free Energies of Organic Solvent and Substrate |
title_sort |
correlation between the activity of candida antarctica lipase b and differences in binding free energies of organic solvent and substrate |
publishDate |
2016 |
url |
https://orbit.dtu.dk/en/publications/2d9ab8bd-5120-4882-85b9-2febd4f69b81 https://doi.org/10.1021/acscatal.6b02073 |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_source |
Banik , S D , Nordblad , M , Woodley , J & Peters , G H J 2016 , ' A Correlation between the Activity of Candida antarctica Lipase B and Differences in Binding Free Energies of Organic Solvent and Substrate ' , ACS Catalysis , vol. 6 , no. 10 , pp. 6350-6361 . https://doi.org/10.1021/acscatal.6b02073 |
op_relation |
https://orbit.dtu.dk/en/publications/2d9ab8bd-5120-4882-85b9-2febd4f69b81 |
op_rights |
info:eu-repo/semantics/closedAccess |
op_doi |
https://doi.org/10.1021/acscatal.6b02073 |
container_title |
ACS Catalysis |
container_volume |
6 |
container_issue |
10 |
container_start_page |
6350 |
op_container_end_page |
6361 |
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1810488441227444224 |