Albany 2019: 20th Conversation - Abstracts

category image Albany 2019
Conversation 20
June 11-15 2019
Adenine Press (2019)

A comparative computational study for deamination of trans and gauche conformers of phenylethylamine in presence of lumiflavin

The deamination of phenylethylamine (PEA) and norepinephrine (NOR) to corresponding aldehyde and ammonia by the enzyme human Monoamine oxidase (hMAO) is one of the most important concerns in neurobiochemistry due to its involvement in several neurological diseases and complications. The enzyme has two isoforms with 70% sequence similarity. Our earlier studies with dopamine-hMAO B showed persistence of trans form at the active site cavity(Dasgupta, Mukherjee, Mukhopadhyay, Banerjee, & Mishra, 2018) whereas MD- simulation followed by DFT studies for phenylethylamine(PEA)-hMAO B complex reveals existence of both trans and gauche conformation for protonated PEA(Dasgupta, Mukherjee, & Mukhopadhyay, 2018). In this work concerted hydride transfer mechanism for trans and gauche conformers of neutral-PEA with lumiflavin moiety (truncated prosthetic group involved during catalysis) have been performed by density functional theory (DFT) methods using B3LYP/DFT-D3 functional with standard split valance basis set 6-31g. This computational work provides the first evidence that could support the easier feasibility of deamination of gauche conformer of hMAO substrates over trans- substrate. The activation energy barrier for trans and gauche PEA are compared, in which gauche conformation is observed to be preferred over trans conformer. The result indicates that the deamination of the neurotransmitters may depend on the conformational preference of phenylethylamine.


This research has been financially supported by ICMR (Project No. ISRM/11 (25)/2017), Government of India.


    Dasgupta, S., Mukherjee, S., & Mukhopadhyay, B. P. (2018). Recognition of trans and gauche phenylethylamine conformers in the active site of human monoamine oxidase B: A MD-simulation and DFT studies. Computational and Theoretical Chemistry, 1127, 44–51.

    Dasgupta, S., Mukherjee, S., Mukhopadhyay, B. P., Banerjee, A., & Mishra, D. K. (2018). Recognition dynamics of dopamine to human Monoamine oxidase B: role of Leu171/Gln206 and conserved water molecules in the active site cavity. Journal of Biomolecular Structure & Dynamics, 36(6), 1439–1462.

Subrata Dasgupta
Soumita Mukherjee
B.P. Mukhopadhyay*

Department of Chemistry
National Institute of Technology
Durgapur-713209 India