Search: onr:"swepub:oai:DiVA.org:uu-195065" >
Structural basis of...
Structural basis of ligand recognition in 5-HT3 receptors
-
Kesters, D. (author)
-
Thompson, A. J. (author)
-
Brams, M. (author)
-
show more...
-
Van Elk, R. (author)
-
Spurny, R. (author)
-
Geitmann, M. (author)
-
Villalgordo, J. M. (author)
-
Guskov, A. (author)
-
- Danielson, Helena U. (author)
- Uppsala universitet,Biokemi
-
Lummis, S. C. R. (author)
-
Smit, A. B. (author)
-
Ulens, C. (author)
-
show less...
-
(creator_code:org_t)
- 2012-11-30
- 2013
- English.
-
In: EMBO Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 14:1, s. 49-56
- Related links:
-
https://doi.org/10.1...
-
show more...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- The 5-HT 3 receptor is a pentameric serotonin-gated ion channel, which mediates rapid excitatory neurotransmission and is the target of a therapeutically important class of anti-emetic drugs, such as granisetron. We report crystal structures of a binding protein engineered to recognize the agonist serotonin and the antagonist granisetron with affinities comparable to the 5-HT 3 receptor. In the serotonin-bound structure, we observe hydrophilic interactions with loop E-binding site residues, which might enable transitions to channel opening. In the granisetron-bound structure, we observe a critical cation-π interaction between the indazole moiety of the ligand and a cationic centre in loop D, which is uniquely present in the 5-HT 3 receptor. We use a series of chemically tuned granisetron analogues to demonstrate the energetic contribution of this electrostatic interaction to high-affinity ligand binding in the human 5-HT 3 receptor. Our study offers the first structural perspective on recognition of serotonin and antagonism by anti-emetics in the 5-HT 3 receptor.
Keyword
- 5-hydroxytryptamine-3 receptor
- Cys-loop receptor
- pentameric ligand-gated ion channel
- serotonin
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Kesters, D.
-
Thompson, A. J.
-
Brams, M.
-
Van Elk, R.
-
Spurny, R.
-
Geitmann, M.
-
show more...
-
Villalgordo, J. ...
-
Guskov, A.
-
Danielson, Helen ...
-
Lummis, S. C. R.
-
Smit, A. B.
-
Ulens, C.
-
show less...
- Articles in the publication
-
EMBO Reports
- By the university
-
Uppsala University