Title:
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Insights on Laccase Engineering from Molecular Simulations: Towards a Binding Focused Strategy
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Author:
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Monza, Emanuele; Lucas, Fatima; Camarero, Susana; Alejaldre, Lorea C.; Martínez, Angel T.; Guallar, Víctor
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Other authors:
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Barcelona Supercomputing Center |
Abstract:
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Understanding the molecular determinants of enzyme performance is of primary importance for the rational design of ad hoc mutants. A novel approach, which combines efficient conformational sampling and quick reactivity scoring, is used here to shed light on how substrate oxidation was improved during the directed evolution experiment of a fungal laccase (from Pycnoporus cinnabarinus), an industrially relevant class of oxidoreductases. It is found that the enhanced activity of the evolved enzyme is mainly the result of substrate arrangement in the active site, with no important change in the redox potential of the T1 copper. Mutations at the active site shift the binding mode into a more buried substrate position and provide a more favorable electrostatic environment for substrate oxidation. As a consequence, engineering the binding event seems to be a viable way to in silico evolution of oxidoreductases. |
Abstract:
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This work has been funded by the EU projects INDOX (KBBE20137613549) and ERC
2009Adg25027PELE (to V.G) and the Spanish Ministry of Education and Science project
CTQ201348287 (to V.G). |
Abstract:
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Peer Reviewed |
Subject(s):
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-Àrees temàtiques de la UPC::Enginyeria mecànica::Impacte ambiental -Oxidation--Methodology -Molecular dynamics -In silico enzyme engineering -Copper oxidoreductases -PELE -Substrate binding -Substrate oxidation -Directed evolution -Dinàmica molecular |
Rights:
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Document type:
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Article - Submitted version Article |
Published by:
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ACS Publications
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