Principles of Cold Adaptation of Fish Lactate Dehydrogenases Revealed by Computer Simulations of the Catalytic Reaction
Abstract Cold-adapted enzymes from psychrophilic and psychrotolerant species are characterized by a higher catalytic activity at low temperature than their mesophilic orthologs and are also usually found to be more thermolabile. Computer simulations of the catalytic reactions have been shown to be a...
Published in: | Molecular Biology and Evolution |
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Oxford University Press (OUP)
2023
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croxfordunivpr:10.1093/molbev/msad099 2024-09-15T17:47:36+00:00 Principles of Cold Adaptation of Fish Lactate Dehydrogenases Revealed by Computer Simulations of the Catalytic Reaction Koenekoop, Lucien Åqvist, Johan Echave, Julian 2023 http://dx.doi.org/10.1093/molbev/msad099 https://academic.oup.com/mbe/advance-article-pdf/doi/10.1093/molbev/msad099/50127039/msad099.pdf https://academic.oup.com/mbe/article-pdf/40/5/msad099/50333902/msad099.pdf en eng Oxford University Press (OUP) https://creativecommons.org/licenses/by-nc/4.0/ Molecular Biology and Evolution volume 40, issue 5 ISSN 0737-4038 1537-1719 journal-article 2023 croxfordunivpr https://doi.org/10.1093/molbev/msad099 2024-07-15T04:24:12Z Abstract Cold-adapted enzymes from psychrophilic and psychrotolerant species are characterized by a higher catalytic activity at low temperature than their mesophilic orthologs and are also usually found to be more thermolabile. Computer simulations of the catalytic reactions have been shown to be a very powerful tool for analyzing the structural and energetic origins of these effects. Here, we examine the cold adaptation of lactate dehydrogenases from two Antarctic and sub-Antarctic fish species using this approach and compare our results with those obtained for the orthologous dogfish enzyme. Direct calculations of thermodynamic activation parameters show that the cold-adapted fish enzymes are characterized by a lower activation enthalpy and a more negative entropy term. This appears to be a universal feature of psychrophilic enzymes, and it is found to originate from a higher flexibility of certain parts of the protein surface. We also carry out free energy simulations that address the differences in thermal stability and substrate binding affinity between the two cold-adapted enzymes, which only differ by a single mutation. These calculations capture the effects previously seen in in vitro studies and provide straightforward explanations of these experimental results. Article in Journal/Newspaper Antarc* Antarctic Oxford University Press Molecular Biology and Evolution 40 5 |
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Open Polar |
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Oxford University Press |
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croxfordunivpr |
language |
English |
description |
Abstract Cold-adapted enzymes from psychrophilic and psychrotolerant species are characterized by a higher catalytic activity at low temperature than their mesophilic orthologs and are also usually found to be more thermolabile. Computer simulations of the catalytic reactions have been shown to be a very powerful tool for analyzing the structural and energetic origins of these effects. Here, we examine the cold adaptation of lactate dehydrogenases from two Antarctic and sub-Antarctic fish species using this approach and compare our results with those obtained for the orthologous dogfish enzyme. Direct calculations of thermodynamic activation parameters show that the cold-adapted fish enzymes are characterized by a lower activation enthalpy and a more negative entropy term. This appears to be a universal feature of psychrophilic enzymes, and it is found to originate from a higher flexibility of certain parts of the protein surface. We also carry out free energy simulations that address the differences in thermal stability and substrate binding affinity between the two cold-adapted enzymes, which only differ by a single mutation. These calculations capture the effects previously seen in in vitro studies and provide straightforward explanations of these experimental results. |
author2 |
Echave, Julian |
format |
Article in Journal/Newspaper |
author |
Koenekoop, Lucien Åqvist, Johan |
spellingShingle |
Koenekoop, Lucien Åqvist, Johan Principles of Cold Adaptation of Fish Lactate Dehydrogenases Revealed by Computer Simulations of the Catalytic Reaction |
author_facet |
Koenekoop, Lucien Åqvist, Johan |
author_sort |
Koenekoop, Lucien |
title |
Principles of Cold Adaptation of Fish Lactate Dehydrogenases Revealed by Computer Simulations of the Catalytic Reaction |
title_short |
Principles of Cold Adaptation of Fish Lactate Dehydrogenases Revealed by Computer Simulations of the Catalytic Reaction |
title_full |
Principles of Cold Adaptation of Fish Lactate Dehydrogenases Revealed by Computer Simulations of the Catalytic Reaction |
title_fullStr |
Principles of Cold Adaptation of Fish Lactate Dehydrogenases Revealed by Computer Simulations of the Catalytic Reaction |
title_full_unstemmed |
Principles of Cold Adaptation of Fish Lactate Dehydrogenases Revealed by Computer Simulations of the Catalytic Reaction |
title_sort |
principles of cold adaptation of fish lactate dehydrogenases revealed by computer simulations of the catalytic reaction |
publisher |
Oxford University Press (OUP) |
publishDate |
2023 |
url |
http://dx.doi.org/10.1093/molbev/msad099 https://academic.oup.com/mbe/advance-article-pdf/doi/10.1093/molbev/msad099/50127039/msad099.pdf https://academic.oup.com/mbe/article-pdf/40/5/msad099/50333902/msad099.pdf |
genre |
Antarc* Antarctic |
genre_facet |
Antarc* Antarctic |
op_source |
Molecular Biology and Evolution volume 40, issue 5 ISSN 0737-4038 1537-1719 |
op_rights |
https://creativecommons.org/licenses/by-nc/4.0/ |
op_doi |
https://doi.org/10.1093/molbev/msad099 |
container_title |
Molecular Biology and Evolution |
container_volume |
40 |
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5 |
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1810497048884019200 |