Pregled bibliografske jedinice broj: 939296
Multiscale simulation of monoamine oxidase catalyzed decomposition of phenylethylamine analogs
Multiscale simulation of monoamine oxidase catalyzed decomposition of phenylethylamine analogs // European journal of pharmacology, 817 (2017), 46-50 doi:10.1016/j.ejphar.2017.05.061 (međunarodna recenzija, članak, znanstveni)
CROSBI ID: 939296 Za ispravke kontaktirajte CROSBI podršku putem web obrasca
Naslov
Multiscale simulation of monoamine oxidase catalyzed decomposition of phenylethylamine analogs
Autori
Oanca, Gabriel ; Stare, Jernej ; Vianello, Robert ; Mavri, Janez
Izvornik
European journal of pharmacology (0014-2999) 817
(2017);
46-50
Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni
Ključne riječi
Monoamine oxidase ; Molecular simulation ; QM/MM methodology ; Empirical valence bond ; Neurotransmitters ; Phenylethylamine
Sažetak
Phenylethylamine (PEA) is an endogenous amphetamine and its levels are increased by physical activity. As other biogenic monoamines, it is decomposed by monoamine oxidase (MAO) enzymes. The chemical mechanism of MAO, and flavoenzymes in general, is a subject of heated debate. We have previously shown that the rate-limiting step of MAO catalysis involves a hydride transfer from the substrate methylene group vicinal to the amino group to the N5 atom of the lumiflavin co-factor moiety. By using multiscale simulation on the Empirical Valence Bond (EVB) level, we studied the chemical reactivity of the monoamine oxidase B catalyzed decomposition of PEA and its two derivatives: p-chloro-β-methylphenylamine (p-CMP) and p-methoxy-β-methylphenethylamine (p-MMP). We calculated activation free energies of 17.1 kcal/mol (PEA), 18.4 kcal/mol (p-MMP) and 20.0 kcal/mol (p-CMP), which are in excellent agreement with the experimental values of 16.7 kcal/mol for PEA and 18.3 kcal/mol for p-MMP, while the experimental value for p-CMP is not available. This gives strong support to the validity of our hydride transfer mechanism for both MAO A and B isoforms. The results are discussed in the context of the interplay between MAO point mutations and neuropsychiatric disorders.
Izvorni jezik
Engleski
Znanstvena područja
Kemija
POVEZANOST RADA
Projekti:
EK-FP7-334493 - Korištenje računalnih tehnika istraživanja biogenih amina u mozgu za liječenje neuroloških bolesti (COMPBAND) (Vianello, Robert, EK ) ( CroRIS)
Ustanove:
Institut "Ruđer Bošković", Zagreb
Profili:
Robert Vianello
(autor)
Citiraj ovu publikaciju:
Časopis indeksira:
- Current Contents Connect (CCC)
- Web of Science Core Collection (WoSCC)
- Science Citation Index Expanded (SCI-EXP)
- SCI-EXP, SSCI i/ili A&HCI
- Scopus
- MEDLINE