Asset Details
Do you wish to reserve the book?
Molecular basis of human noradrenaline transporter reuptake and inhibition
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Molecular basis of human noradrenaline transporter reuptake and inhibition
Do you wish to request the book?
Molecular basis of human noradrenaline transporter reuptake and inhibition
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Molecular basis of human noradrenaline transporter reuptake and inhibition
2024
Overview
Noradrenaline, also known as norepinephrine, has a wide range of activities and effects on most brain cell types
1
. Its reuptake from the synaptic cleft heavily relies on the noradrenaline transporter (NET) located in the presynaptic membrane
2
. Here we report the cryo-electron microscopy (cryo-EM) structures of the human NET in both its apo state and when bound to substrates or antidepressant drugs, with resolutions ranging from 2.5 Å to 3.5 Å. The two substrates, noradrenaline and dopamine, display a similar binding mode within the central substrate binding site (S1) and within a newly identified extracellular allosteric site (S2). Four distinct antidepressants, namely, atomoxetine, desipramine, bupropion and escitalopram, occupy the S1 site to obstruct substrate transport in distinct conformations. Moreover, a potassium ion was observed within sodium-binding site 1 in the structure of the NET bound to desipramine under the KCl condition. Complemented by structural-guided biochemical analyses, our studies reveal the mechanism of substrate recognition, the alternating access of NET, and elucidate the mode of action of the four antidepressants.
The cryo-electron microscopy structures of the human noradrenaline transporter in both the apo state and bound to substrates or antidepressant drugs are resolved.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 82/16
/ 82/29
/ 82/80
/ 82/83
/ Antidepressive Agents - chemistry
/ Antidepressive Agents - metabolism
/ Antidepressive Agents - pharmacology
/ Atomoxetine Hydrochloride - chemistry
/ Atomoxetine Hydrochloride - metabolism
/ Atomoxetine Hydrochloride - pharmacology
/ Dopamine
/ Humanities and Social Sciences
/ Humans
/ Norepinephrine Plasma Membrane Transport Proteins - antagonists & inhibitors
/ Norepinephrine Plasma Membrane Transport Proteins - chemistry
/ Norepinephrine Plasma Membrane Transport Proteins - metabolism
/ Proteins
/ Science
/ Sodium
