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PDBsum entry 7dfp
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Membrane protein
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PDB id
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7dfp
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Contents |
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335 a.a.
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215 a.a.
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220 a.a.
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References listed in PDB file
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Key reference
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Title
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Structure of the dopamine d2 receptor in complex with the antipsychotic drug spiperone.
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Authors
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D.Im,
A.Inoue,
T.Fujiwara,
T.Nakane,
Y.Yamanaka,
T.Uemura,
C.Mori,
Y.Shiimura,
K.T.Kimura,
H.Asada,
N.Nomura,
T.Tanaka,
A.Yamashita,
E.Nango,
K.Tono,
F.M.N.Kadji,
J.Aoki,
S.Iwata,
T.Shimamura.
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Ref.
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Nat Commun, 2020,
11,
6442.
[DOI no: ]
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PubMed id
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Abstract
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In addition to the serotonin 5-HT2A receptor (5-HT2AR),
the dopamine D2 receptor (D2R) is a key therapeutic target
of antipsychotics for the treatment of schizophrenia. The inactive state
structures of D2R have been described in complex with the inverse
agonists risperidone (D2Rris) and haloperidol
(D2Rhal). Here we describe the structure of human
D2R in complex with spiperone (D2Rspi). In
D2Rspi, the conformation of the extracellular loop (ECL)
2, which composes the ligand-binding pocket, was substantially different from
those in D2Rris and D2Rhal,
demonstrating that ECL2 in D2R is highly dynamic. Moreover,
D2Rspi exhibited an extended binding pocket to accommodate
spiperone's phenyl ring, which probably contributes to the selectivity of
spiperone to D2R and 5-HT2AR. Together with
D2Rris and D2Rhal, the structural
information of D2Rspi should be of value for designing
novel antipsychotics with improved safety and efficacy.
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