Substrate Conformations Set the Rate of Enzymatic Acrylation by Lipases
Abstract Acrylates represent a class of α,β‐unsaturated compounds of high industrial importance. We investigated the influence of substrate conformations on the experimentally determined reaction rates of the enzyme‐catalysed transacylation of methyl acrylate and derivatives by ab initio DFT B3LYP c...
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crwiley:10.1002/cbic.200900758 2024-06-02T07:57:14+00:00 Substrate Conformations Set the Rate of Enzymatic Acrylation by Lipases Syrén, Per‐Olof Hult, Karl 2010 http://dx.doi.org/10.1002/cbic.200900758 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fcbic.200900758 http://onlinelibrary.wiley.com/wol1/doi/10.1002/cbic.200900758/fullpdf en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor ChemBioChem volume 11, issue 6, page 802-810 ISSN 1439-4227 1439-7633 journal-article 2010 crwiley https://doi.org/10.1002/cbic.200900758 2024-05-03T11:32:17Z Abstract Acrylates represent a class of α,β‐unsaturated compounds of high industrial importance. We investigated the influence of substrate conformations on the experimentally determined reaction rates of the enzyme‐catalysed transacylation of methyl acrylate and derivatives by ab initio DFT B3LYP calculations and molecular dynamics simulations. The results supported a least‐motion mechanism upon the sp 2 to sp 3 substrate transition to reach the transition state in the enzyme active site. This was in accordance with our hypothesis that acrylates form productive transition states from their low‐energy s‐ sis /s‐ trans conformations. Apparent k cat values were measured for Candida antarctica lipase B (CALB), Humicola insolens cutinase and Rhizomucor miehei lipase and were compared to results from computer simulations. More potent enzymes for acryltransfer, such as the CALB mutant V190A and acrylates with higher turnover numbers, showed elevated populations of productive transition states. Article in Journal/Newspaper Antarc* Antarctica Wiley Online Library ChemBioChem 11 6 802 810 |
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English |
description |
Abstract Acrylates represent a class of α,β‐unsaturated compounds of high industrial importance. We investigated the influence of substrate conformations on the experimentally determined reaction rates of the enzyme‐catalysed transacylation of methyl acrylate and derivatives by ab initio DFT B3LYP calculations and molecular dynamics simulations. The results supported a least‐motion mechanism upon the sp 2 to sp 3 substrate transition to reach the transition state in the enzyme active site. This was in accordance with our hypothesis that acrylates form productive transition states from their low‐energy s‐ sis /s‐ trans conformations. Apparent k cat values were measured for Candida antarctica lipase B (CALB), Humicola insolens cutinase and Rhizomucor miehei lipase and were compared to results from computer simulations. More potent enzymes for acryltransfer, such as the CALB mutant V190A and acrylates with higher turnover numbers, showed elevated populations of productive transition states. |
format |
Article in Journal/Newspaper |
author |
Syrén, Per‐Olof Hult, Karl |
spellingShingle |
Syrén, Per‐Olof Hult, Karl Substrate Conformations Set the Rate of Enzymatic Acrylation by Lipases |
author_facet |
Syrén, Per‐Olof Hult, Karl |
author_sort |
Syrén, Per‐Olof |
title |
Substrate Conformations Set the Rate of Enzymatic Acrylation by Lipases |
title_short |
Substrate Conformations Set the Rate of Enzymatic Acrylation by Lipases |
title_full |
Substrate Conformations Set the Rate of Enzymatic Acrylation by Lipases |
title_fullStr |
Substrate Conformations Set the Rate of Enzymatic Acrylation by Lipases |
title_full_unstemmed |
Substrate Conformations Set the Rate of Enzymatic Acrylation by Lipases |
title_sort |
substrate conformations set the rate of enzymatic acrylation by lipases |
publisher |
Wiley |
publishDate |
2010 |
url |
http://dx.doi.org/10.1002/cbic.200900758 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fcbic.200900758 http://onlinelibrary.wiley.com/wol1/doi/10.1002/cbic.200900758/fullpdf |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_source |
ChemBioChem volume 11, issue 6, page 802-810 ISSN 1439-4227 1439-7633 |
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http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1002/cbic.200900758 |
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ChemBioChem |
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11 |
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6 |
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802 |
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810 |
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1800740121334513664 |