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01-11-2018 | Neurology and Preclinical Neurological Studies - Review Article

The structure of monoamine oxidases: past, present, and future

Authors: Luca Giacinto Iacovino, Francesca Magnani, Claudia Binda

Published in: Journal of Neural Transmission | Issue 11/2018

Abstract

The first crystal structure of mammalian monoamine oxidases (MAOs) was solved in 2002; almost 65 years after, these FAD-dependent enzymes were discovered and classified as responsible for the oxidation of aromatic neurotransmitters. Both MAO A and MAO B feature a two-domain topology characterized by the Rossmann fold, interacting with dinucleotide cofactors, which is intimately associated to a substrate-binding domain. This globular body is endowed with a C-terminal α-helix that anchors the protein to the outer mitochondrial phospholipid bilayer. As monotopic membrane proteins, the structural elucidation of MAOs was a challenging task that required the screening of different detergent conditions for their purification and crystallization. MAO A and MAO B structures differ both in their oligomerization architecture and in details of their active sites. Purified human MAO B and rat MAO A are dimeric, whereas human MAO A was found to be monomeric, which is believed to result from the detergent treatments used to extract the protein from the membrane. The active site of MAOs consists of a hydrophobic cavity located in front of the flavin cofactor and extending to the protein surface. Some structural features are highly conserved in the two isozymes, such as a Tyr–Tyr aromatic sandwich in front of the flavin ring and a Lys residue hydrogen-bonded to the cofactor N5 atom, whereas a pair of gating residues (Phe208/Ile335 in MAO A; Ile199/Tyr326 in MAO B) specifically determines the different substrate and inhibitor properties of the two enzymes.

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Title: The structure of monoamine oxidases: past, present, and future
Authors: Luca Giacinto Iacovino
Francesca Magnani
Claudia Binda
Publication date: 01-11-2018
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 11/2018
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-018-1915-z

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The structure of monoamine oxidases: past, present, and future

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