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Open AccessArticle

Structure Modeling of the Norepinephrine Transporter

Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Cracow, Poland
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(1), 102;
Received: 4 December 2019 / Revised: 31 December 2019 / Accepted: 3 January 2020 / Published: 7 January 2020
(This article belongs to the Special Issue Advances in Membrane Proteins)
The norepinephrine transporter (NET) is one of the monoamine transporters. Its X-ray crystal structure has not been obtained yet. Inhibitors of human NET (hNET) play a major role in the treatment of many central and peripheral nervous system diseases. In this study, we focused on the spatial structure of a NET constructed by homology modeling on Drosophila melanogaster dopamine transporter templates. We further examined molecular construction of primary binding pocket (S1) together with secondary binding site (S2) and extracellular loop 4 (EL4). The next stage involved docking of transporter inhibitors: Reboxetine, duloxetine, desipramine, and other commonly used drugs. The procedure revealed the molecular orientation of residues and disclosed ones that are the most important for ligand binding: Phenylalanine F72, aspartic acid D75, tyrosine Y152, and phenylalanine F317. Aspartic acid D75 plays a key role in recognition of the basic amino group present in monoamine transporter inhibitors and substrates. The study also presents a comparison of hNET models with other related proteins, which could provide new insights into their interaction with therapeutics and aid future development of novel bioactive compounds. View Full-Text
Keywords: norepinephrine transporter; homology modeling; ligand docking; reuptake inhibitors norepinephrine transporter; homology modeling; ligand docking; reuptake inhibitors
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MDPI and ACS Style

Góral, I.; Łątka, K.; Bajda, M. Structure Modeling of the Norepinephrine Transporter. Biomolecules 2020, 10, 102.

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