Target Binding Site Detail

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Target General Information
Ligand General Information
Drug Binding Sites of Target
References
Target General Information  Top
Target ID T22118 Target Info
Target Name Dopamine D1 receptor (D1R)
Synonyms D(1A) dopamine receptor
Target Type Successful Target
Gene Name DRD1
Biochemical Class GPCR rhodopsin
UniProt ID
DRD1_HUMAN
Ligand General Information  Top
Ligand Name Mevidalen Ligand Info
Canonical SMILES CC1C2=CC=CC(=C2CC(N1C(=O)CC3=C(C=CC=C3Cl)Cl)CO)CCC(C)(C)O
InChI 1S/C24H29Cl2NO3/c1-15-18-7-4-6-16(10-11-24(2,3)30)19(18)12-17(14-28)27(15)23(29)13-20-21(25)8-5-9-22(20)26/h4-9,15,17,28,30H,10-14H2,1-3H3/t15-,17+/m0/s1
InChIKey XHCSBQBBGNQINS-DOTOQJQBSA-N
PubChem Compound ID 86290953
Drug Binding Sites of Target  Top
PDB ID: 7CKZ      Cryo-EM structure of Dopamine and LY3154207 bound dopamine receptor DRD1-Gs signaling complex
Method Electron microscopy Resolution 3.10 Å Mutation Yes [1]
PDB Sequence
FSVRILTACF
29
LSLLILSTLL
39
GNTLVCAAVI
49
RFRHLRSKVT
59
NFFVISLAVS
69

DLLVAVLVMP
79
WKAVAEIAGF
89
WPFGSFCNIW
99
VAFDIMCSTA
109
SILNLCVISV
119

DRYWAISSPF
129
RYERKMTPKA
139
AFILISVAWT
149
LSVLISFIPV
159
QLSWHKANCD
187

SSLSRTYAIS
197
SSVISFYIPV
207
AIMIVTYTRI
217
YRIAQKQIRR
227
IAALERAAVH
237

SFKRETKVLK
272
TLSVIMGVFV
282
CCWLPFFILN
292
CILPFCFCID
309
SNTFDVFVWF
319

GWANSSLNPI
329
IYAFNADFRK
339
AFSTL
Residue
Distance (Å)
LEU112
2.352
CYS115
2.703
VAL116
4.727
VAL119
2.912
TRP123
2.421
ARG130
3.585
Residue
Distance (Å)
LEU143
3.926
VAL146
4.207
ALA147
4.959
LEU150
4.591
ILE209
3.697
PDB ID: 7X2F      Cryo-EM structure of the dopamine and LY3154207-bound D1 dopamine receptor and mini-Gs complex
Method Electron microscopy Resolution 3.00 Å Mutation Yes [2]
PDB Sequence
SVRILTACFL
30
SLLILSTLLG
40
NTLVCAAVIR
50
FRHLRSKVTN
60
FFVISLAVSD
70

LLVAVLVMPW
80
KAVAEIAGFW
90
PFGSFCNIWV
100
AFDIMCSTAS
110
ILNLCVISVD
120

RYWAISSPFR
130
YERKMTPKAA
140
FILISVAWTL
150
SVLISFIPVQ
160
LSWHKAKDNC
186

DSSLSRTYAI
196
SSSVISFYIP
206
VAIMIVTYTR
216
IYRIAQKQIR
226
RIAALERAAV
236

HAKNCFKRET
268
KVLKTLSVIM
278
GVFVCCWLPF
288
FILNCILPFC
298
GFCIDSNTFD
314

VFVWFGWANS
324
SLNPIIYAFN
334
ADFRKAFSTL
344
LG
Residue
Distance (Å)
TRP123
3.663
SER127
3.012
ARG130
3.311
TYR131
4.062
LYS134
3.611
MET135
4.011
Residue
Distance (Å)
THR136
4.840
LYS138
2.506
ALA139
3.566
ILE142
3.694
LEU143
3.681
PDB ID: 7LJC      Allosteric modulator LY3154207 binding to SKF-81297-bound dopamine receptor 1 in complex with miniGs protein
Method Electron microscopy Resolution 3.00 Å Mutation No [3]
PDB Sequence
SVRILTACFL
30
SLLILSTLLG
40
NTLVCAAVIR
50
FRHLRSKVTN
60
FFVISLAVSD
70

LLVAVLVMPW
80
KAVAEIAGFW
90
PFGSFCNIWV
100
AFDIMCSTAS
110
ILNLCVISVD
120

RYWAISSPFR
130
YERKMTPKAA
140
FILISVAWTL
150
SVLISFIPVQ
160
LSWHKAKPNC
186

DSSLSRTYAI
196
SSSVISFYIP
206
VAIMIVTYTR
216
IYRIAQKQIR
226
RIAALERAAV
236

HAKNFKRETK
269
VLKTLSVIMG
279
VFVCCWLPFF
289
ILNCILPFCC
307
IDSNTFDVFV
317

WFGWANSSLN
327
PIIYAFNADF
337
RKAFSTLLGC
347
Residue
Distance (Å)
TRP123
3.391
SER127
3.605
ARG130
2.965
TYR131
3.908
LYS134
3.660
Residue
Distance (Å)
MET135
3.810
LYS138
2.667
ALA139
4.007
ILE142
3.801
LEU143
4.141
PDB ID: 7LJD      Allosteric modulator LY3154207 binding to dopamine-bound dopamine receptor 1 in complex with miniGs protein
Method Electron microscopy Resolution 3.20 Å Mutation No [3]
PDB Sequence
SVRILTACFL
30
SLLILSTLLG
40
NTLVCAAVIR
50
FRHLRSKVTN
60
FFVISLAVSD
70

LLVAVLVMPW
80
KAVAEIAGFW
90
PFGSFCNIWV
100
AFDIMCSTAS
110
ILNLCVISVD
120

RYWAISSPFR
130
YERKMTPKAA
140
FILISVAWTL
150
SVLISFIPVQ
160
LSWHKAKPID
184

NCDSSLSRTY
194
AISSSVISFY
204
IPVAIMIVTY
214
TRIYRIAQKQ
224
IRRIAALERA
234

AVHAKNCQFK
265
RETKVLKTLS
275
VIMGVFVCCW
285
LPFFILNCIL
295
PFCCIDSNTF
313

DVFVWFGWAN
323
SSLNPIIYAF
333
NADFRKAFST
343
LLGCY
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .G4C or .G4C2 or .G4C3 or :3G4C;style chemicals stick;color identity;select .R:123 or .R:127 or .R:130 or .R:131 or .R:134 or .R:135 or .R:138 or .R:139 or .R:142 or .R:143; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
TRP123
3.594
SER127
3.826
ARG130
3.026
TYR131
4.106
LYS134
3.949
Residue
Distance (Å)
MET135
3.809
LYS138
3.022
ALA139
3.778
ILE142
3.811
LEU143
4.090
References  Top
REF 1 Ligand recognition and allosteric regulation of DRD1-Gs signaling complexes. Cell. 2021 Feb 18;184(4):943-956.e18.
REF 2 Ligand recognition and biased agonism of the D1 dopamine receptor. Nat Commun. 2022 Jun 8;13(1):3186.
REF 3 Mechanism of dopamine binding and allosteric modulation of the human D1 dopamine receptor. Cell Res. 2021 May;31(5):593-596.

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