Hidden Conformations in Aspergillus niger Monoamine Oxidase are Key for Catalytic Efficiency

Enzymes exist as an ensemble of conformational states, whose populations can be shifted by substrate binding, allosteric interactions, but also by introducing mutations to their sequence. Tuning the populations of the enzyme conformational states through mutation enables evolution towards novel acti...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2019-03, Vol.58 (10), p.3097-3101
Main Authors: Curado‐Carballada, Christian, Feixas, Ferran, Iglesias‐Fernández, Javier, Osuna, Sílvia
Format: Article
Language:English
Subjects:
Allosteric properties
Amine oxidase (flavin-containing)
Aspergillus niger
Binding
Catalysis
distal mutations
Enzymatic activity
Enzyme activity
enzyme catalysis
Enzymes
Markov chains
molecular dynamics
monoamine oxidase
Mutation
Oxidase
Populations
substrate binding
Substrates
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Summary:Enzymes exist as an ensemble of conformational states, whose populations can be shifted by substrate binding, allosteric interactions, but also by introducing mutations to their sequence. Tuning the populations of the enzyme conformational states through mutation enables evolution towards novel activity. Herein, Markov state models are used to unveil hidden conformational states of monoamine oxidase from Aspergillus niger (MAO‐N). These hidden conformations, not previously observed by any other technique, play a crucial role in substrate binding and enzyme activity. This reveals how distal mutations regulate MAO‐N activity by stabilizing these hidden, catalytically important conformational states, but also by modulating the communication pathway between both MAO‐N subunits. Hide and seek: Markov state models are used to unveil hidden conformational states of Monoamine Oxidase from Aspergillus niger (MAO‐N). These hidden conformations, not previously observed by any other technique, play a crucial role in the enzyme activity and substrate binding. This reveals how distal mutations regulate MAO‐N activity by stabilizing these hidden, catalytically important conformational states.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201812532