2YMD

Crystal structure of a mutant binding protein (5HTBP-AChBP) in complex with serotonin (5-hydroxytryptamine)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.96 Å
  • R-Value Free: 0.201 
  • R-Value Work: 0.159 
  • R-Value Observed: 0.160 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Structural Basis of Ligand Recognition in 5-Ht(3) Receptors.

Kesters, D.Thompson, A.J.Brams, M.Van Elk, R.Spurny, R.Geitmann, M.Villalgordo, J.M.Guskov, A.Helena Danielson, U.Lummis, S.C.Smit, A.B.Ulens, C.

(2013) EMBO Rep 14: 49

  • DOI: https://doi.org/10.1038/embor.2012.189
  • Primary Citation of Related Structures:  
    2YMD, 2YME

  • PubMed Abstract: 

    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.


  • Organizational Affiliation

    Laboratory of Structural Neurobiology, KULeuven, Leuven, Belgium.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
SOLUBLE ACETYLCHOLINE RECEPTOR
A, B, C, D, E
A, B, C, D, E, F, G, H, I, J
212Aplysia californicaMutation(s): 1 
UniProt
Find proteins for Q8WSF8 (Aplysia californica)
Explore Q8WSF8 
Go to UniProtKB:  Q8WSF8
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8WSF8
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SRO
Query on SRO

Download Ideal Coordinates CCD File 
AA [auth E]
EA [auth F]
IA [auth G]
K [auth A]
LA [auth H]
AA [auth E],
EA [auth F],
IA [auth G],
K [auth A],
LA [auth H],
NA [auth I],
O [auth B],
PA [auth J],
S [auth C],
W [auth D]
SEROTONIN
C10 H12 N2 O
QZAYGJVTTNCVMB-UHFFFAOYSA-N
PO4
Query on PO4

Download Ideal Coordinates CCD File 
CA [auth E]
GA [auth F]
JA [auth G]
M [auth A]
MA [auth H]
CA [auth E],
GA [auth F],
JA [auth G],
M [auth A],
MA [auth H],
OA [auth I],
Q [auth B],
QA [auth J],
U [auth C],
Z [auth D]
PHOSPHATE ION
O4 P
NBIIXXVUZAFLBC-UHFFFAOYSA-K
GOL
Query on GOL

Download Ideal Coordinates CCD File 
BA [auth E]
DA [auth F]
FA [auth F]
HA [auth F]
KA [auth G]
BA [auth E],
DA [auth F],
FA [auth F],
HA [auth F],
KA [auth G],
L [auth A],
N [auth B],
P [auth B],
R [auth B],
RA [auth J],
T [auth C],
V [auth D],
X [auth D],
Y [auth D]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
SRO PDBBind:  2YMD Kd: 6.93e+5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.96 Å
  • R-Value Free: 0.201 
  • R-Value Work: 0.159 
  • R-Value Observed: 0.160 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 203.565α = 90
b = 140.064β = 99.08
c = 126.528γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
SCALAdata scaling
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2012-12-12
    Type: Initial release
  • Version 1.1: 2013-01-30
    Changes: Database references
  • Version 1.2: 2023-12-20
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description
  • Version 1.3: 2024-11-13
    Changes: Structure summary