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Hidden Conformations in Aspergillus niger Monoamine Oxidase are Key for Catalytic Efficiency
Author(s) -
CuradoCarballada Christian,
Feixas Ferran,
IglesiasFernández Javier,
Osuna Sílvia
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201812532
Subject(s) - allosteric regulation , monoamine oxidase , chemistry , aspergillus niger , enzyme , stereochemistry , substrate (aquarium) , mutation , conformational change , biochemistry , biophysics , biology , gene , ecology
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.