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 2019-03, Vol.131 (10), p.3129-3133
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
Chemistry
Distale Mutationen
Enzymatic activity
Enzyme activity
Enzymes
Enzymkatalyse
Markov chains
Moleküldynamik
Monoamin-Oxidase
Mutation
Oxidase
Populations
Substratbindung
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. Nichts zu verbergen: Markov‐Zustandsmodelle werden verwendet, um verborgene Konformationszustände der Monoamin‐Oxidase in Aspergillus niger (MAO‐N) aufzudecken. Diese verborgenen Konformationen, die vorher nicht mit anderen Techniken beobachtet wurden, spielen eine entscheidende Rolle für die Enzymaktivität und Substratbindung und zeigen, wie distale Mutationen die MAO‐N‐Aktivität regulieren.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.201812532