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PDBsum entry 2wn9
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Contents |
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* Residue conservation analysis
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PDB id:
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Receptor
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Title:
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Crystal structure of aplysia achbp in complex with 4-0h-dmxba
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Structure:
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Soluble acetylcholine receptor. Chain: a, b, c, d, e. Fragment: residues 18-236. Synonym: acetylcholine binding protein. Engineered: yes
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Source:
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Aplysia californica. California sea hare. Organism_taxid: 6500. Cell: sensory cell. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293
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Resolution:
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1.75Å
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R-factor:
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0.171
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R-free:
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0.203
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Authors:
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G.Sulzenbacher,R.Hibbs,J.Shi,T.Talley,S.Conrod,W.Kem,P.Taylor, P.Marchot,Y.Bourne
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Key ref:
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R.E.Hibbs
et al.
(2009).
Structural determinants for interaction of partial agonists with acetylcholine binding protein and neuronal alpha7 nicotinic acetylcholine receptor.
Embo J,
28,
3040-3051.
PubMed id:
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Date:
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07-Jul-09
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Release date:
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01-Sep-09
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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.
209 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 1 residue position (black
cross)
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Embo J
28:3040-3051
(2009)
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PubMed id:
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Structural determinants for interaction of partial agonists with acetylcholine binding protein and neuronal alpha7 nicotinic acetylcholine receptor.
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R.E.Hibbs,
G.Sulzenbacher,
J.Shi,
T.T.Talley,
S.Conrod,
W.R.Kem,
P.Taylor,
P.Marchot,
Y.Bourne.
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ABSTRACT
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The pentameric acetylcholine-binding protein (AChBP) is a soluble surrogate of
the ligand binding domain of nicotinic acetylcholine receptors. Agonists bind
within a nest of aromatic side chains contributed by loops C and F on opposing
faces of each subunit interface. Crystal structures of Aplysia AChBP bound with
the agonist anabaseine, two partial agonists selectively activating the alpha7
receptor, 3-(2,4-dimethoxybenzylidene)-anabaseine and its 4-hydroxy metabolite,
and an indole-containing partial agonist, tropisetron, were solved at 2.7-1.75 A
resolution. All structures identify the Trp 147 carbonyl oxygen as the hydrogen
bond acceptor for the agonist-protonated nitrogen. In the partial agonist
complexes, the benzylidene and indole substituent positions, dictated by tight
interactions with loop F, preclude loop C from adopting the closed conformation
seen for full agonists. Fluctuation in loop C position and duality in ligand
binding orientations suggest molecular bases for partial agonism at full-length
receptors. This study, while pointing to loop F as a major determinant of
receptor subtype selectivity, also identifies a new template region for
designing alpha7-selective partial agonists to treat cognitive deficits in
mental and neurodegenerative disorders.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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J.D.Durrant,
and
J.A.McCammon
(2011).
BINANA: a novel algorithm for ligand-binding characterization.
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J Mol Graph Model,
29,
888-893.
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M.Brams,
A.Pandya,
D.Kuzmin,
R.van Elk,
L.Krijnen,
J.L.Yakel,
V.Tsetlin,
A.B.Smit,
and
C.Ulens
(2011).
A structural and mutagenic blueprint for molecular recognition of strychnine and d-tubocurarine by different cys-loop receptors.
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PLoS Biol,
9,
e1001034.
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PDB codes:
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T.Sander,
B.Frølund,
A.T.Bruun,
I.Ivanov,
J.A.McCammon,
and
T.Balle
(2011).
New insights into the GABA(A) receptor structure and orthosteric ligand binding: receptor modeling guided by experimental data.
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Proteins,
79,
1458-1477.
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A.J.Thompson,
H.A.Lester,
and
S.C.Lummis
(2010).
The structural basis of function in Cys-loop receptors.
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Q Rev Biophys,
43,
449-499.
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P.Taylor
(2010).
Defining the determinants of nicotine selectivity.
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Proc Natl Acad Sci U S A,
107,
13195-13196.
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Y.Bourne,
Z.Radic,
R.Aráoz,
T.T.Talley,
E.Benoit,
D.Servent,
P.Taylor,
J.Molgó,
and
P.Marchot
(2010).
Structural determinants in phycotoxins and AChBP conferring high affinity binding and nicotinic AChR antagonism.
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Proc Natl Acad Sci U S A,
107,
6076-6081.
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PDB codes:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
