5MRL

Crystal structure of human monoamine oxidase B (MAO B) in complex with N(Furan2ylmethyl)Nmethylprop2yn1amine (F2MPA)

Summary for 5MRL

• Entry DOI: 10.2210/pdb5mrl/pdb
• Descriptor: Amine oxidase [flavin-containing] B, FLAVIN-ADENINE DINUCLEOTIDE, (~{E})-~{N}-(furan-2-ylmethyl)-~{N}-methyl-prop-1-en-1-amine, ... (4 entities in total)
• Functional Keywords: monoamine oxidase, neurodegeneration, inhibitor, enzyme, oxidoreductase
• Biological source: Homo sapiens (Human)
• Cellular location: Mitochondrion outer membrane; Single-pass type IV membrane protein; Cytoplasmic side: P27338
• Total number of polymer chains: 2
• Total formula weight: 119548.97

Authors

Binda, C.,De Deurwaerdere, P.,Corne, R.,Leone, C.,Valeri, A.,Valoti, M.,Ramsay, R.R.,Fall, Y.,Marco-Contelles, J. (deposition date: 2016-12-23, release date: 2017-01-11, Last modification date: 2024-11-13)

Primary citation

De Deurwaerdere, P.,Binda, C.,Corne, R.,Leone, C.,Valeri, A.,Valoti, M.,Ramsay, R.R.,Fall, Y.,Marco-Contelles, J.
Comparative Analysis of the Neurochemical Profile and MAO Inhibition Properties of N-(Furan-2-ylmethyl)-N-methylprop-2-yn-1-amine.
ACS Chem Neurosci, 8:1026-1035, 2017

PubMed Abstract: The regulation of brain monoamine levels is paramount for cognitive functions, and the monoamine oxidase (MAO A and B) enzymes play a central role in these processes. The aim of this study was to evaluate whether the procognitive properties exerted by propargylamine N-(furan-2-ylmethyl)-N-methylprop-2-yn-1-amine (F2MPA) are related to changes in monoamine content via MAO inhibition. In vivo microdialysis and ex vivo amine metabolite measurement demonstrated region-specific alterations in monoamine metabolism that differ from both of the classic MAO A and MAO B inhibitors, clorgyline and l-deprenyl, respectively. Although all the inhibitors (1 and 4 mg/kg) increased cortical serotonin tissue content, only F2MPA increased the levels of cortical noradrenaline. In the striatum, clorgyline (1 mg/kg), but not F2MPA (1 mg/kg), reduced extracellular levels of dopamine metabolites at rest or stimulated by the intrastriatal application of the MAO substrate 3-methoxytyramine. In vitro, F2MPA exhibited a low affinity toward MAO B and MAO A. Nonetheless, it modified the B form of MAO, forming a flavin adduct structurally similar to that with deprenyl. F2MPA was rapidly metabolized in the presence of rat but not human microsomes, producing a hydroxylated derivative. In conclusion, the effect of F2MPA on cognition may arise from monoaminergic changes in the cortex, but the role of MAO in this process is likely to be negligible, consistent with the poor affinity of F2MPA for MAO.

PubMed: 27977122
DOI: 10.1021/acschemneuro.6b00377

Experimental method

X-RAY DIFFRACTION (2.42 Å)