Hidden Conformations in Aspergillus niger Monoamine Oxidase are Key for Catalytic Efficiency.
distal mutations
enzyme catalysis
molecular dynamics
monoamine oxidase
substrate binding
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
04 03 2019
04 03 2019
Historique:
received:
31
10
2018
pubmed:
3
1
2019
medline:
28
8
2020
entrez:
3
1
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30600584
doi: 10.1002/anie.201812532
doi:
Substances chimiques
Fungal Proteins
0
Monoamine Oxidase
EC 1.4.3.4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3097-3101Subventions
Organisme : H2020 European Research Council
ID : ERC-2015-StG-679001
Pays : International
Organisme : H2020 Marie Skłodowska-Curie Actions
ID : H2020-MSCA-IF-2016-753045
Pays : International
Organisme : H2020 Marie Skłodowska-Curie Actions
ID : MSCA-IF-2014-EF-661160
Pays : International
Organisme : Agència de Gestió d'Ajuts Universitaris i de Recerca
ID : 2017 SGR-1707
Pays : International
Organisme : MINECO
ID : CTQ2014-59212-P
Pays : International
Organisme : MINECO
ID : RYC-2014-16846
Pays : International
Organisme : Marie Skłodowska-Curie Actions
ID : PCIG14-GA-2013-630978
Pays : International
Informations de copyright
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.