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PDBsum entry 2ymd
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PDB id:
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Receptor
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Title:
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Crystal structure of a mutant binding protein (5htbp-achbp) in complex with serotonin (5-hydroxytryptamine)
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Structure:
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Soluble acetylcholine receptor. Chain: a, b, c, d, e, f, g, h, i, j. Fragment: acetylcholine binding domain, residues 20-231. Synonym: achbp. Engineered: yes. Mutation: yes
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Source:
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Aplysia californica. California sea hare. Organism_taxid: 6500. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
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Resolution:
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1.96Å
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R-factor:
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0.160
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R-free:
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0.201
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Authors:
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D.Kesters,A.J.Thompson,M.Brams,R.V.Elk,R.Spurny,M.Geitmann, J.M.Villalgordo,A.Guskov,U.H.Danielson,S.C.R.Lummis,A.B.Smit,C.Ulens
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Key ref:
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D.Kesters
et al.
(2013).
Structural basis of ligand recognition in 5-HT3 receptors.
Embo Rep,
14,
49-56.
PubMed id:
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Date:
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09-Oct-12
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Release date:
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12-Dec-12
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PROCHECK
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Headers
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References
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Q8WSF8
(Q8WSF8_APLCA) -
Soluble acetylcholine receptor from Aplysia californica
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Seq:
Struc:
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236 a.a.
212 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 6 residue positions (black
crosses)
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Embo Rep
14:49-56
(2013)
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PubMed id:
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Structural basis of ligand recognition in 5-HT3 receptors.
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D.Kesters,
A.J.Thompson,
M.Brams,
R.van Elk,
R.Spurny,
M.Geitmann,
J.M.Villalgordo,
A.Guskov,
U.H.Danielson,
S.C.Lummis,
A.B.Smit,
C.Ulens.
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ABSTRACT
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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.
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