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

Journal of Neural Transmission
Luca Giacinto IacovinoClaudia Binda

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...Continue Reading

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Citations

Feb 1, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Paolo GuglielmiJacobus P Petzer
May 15, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Najla O ZarmouhKaram F A Soliman
Oct 6, 2020·Frontiers in Cell and Developmental Biology·Qiuyue XuBin Yuan
Feb 11, 2020·Frontiers in Pharmacology·Miguel Reyes-ParadaBruce K Cassels
Nov 3, 2020·Chemical & Pharmaceutical Bulletin·Koichi TakaoYoshiaki Sugita
Jun 27, 2020·ACS Chemical Biology·Luca Giacinto IacovinoClaudia Binda
May 18, 2021·Frontiers in Pharmacology·Mahyar Ostadkarampour, Edward E Putnins
Jun 14, 2021·Bioorganic & Medicinal Chemistry·Koichi TakaoYoshiaki Sugita
Jul 25, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Tjaša MazejMatej Sova
Apr 29, 2020·Combinatorial Chemistry & High Throughput Screening·Nisha A RehumanHoon Kim

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