Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T52522 | Target Info | |||
| Target Name | Adrenergic receptor beta-2 (ADRB2) | ||||
| Synonyms | Beta-2 adrenoreceptor; Beta-2 adrenoceptor; Beta-2 adrenergic receptor; B2AR; ADRB2R | ||||
| Target Type | Successful Target | ||||
| Gene Name | ADRB2 | ||||
| Biochemical Class | GPCR rhodopsin | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | 8-[(1r)-2-{[1,1-Dimethyl-2-(2-Methylphenyl)ethyl]amino}-1-Hydroxyethyl]-5-Hydroxy-2h-1,4-Benzoxazin-3(4h)-One | Ligand Info | |||
| Canonical SMILES | CC1=CC=CC=C1CC(C)(C)NCC(C2=C3C(=C(C=C2)O)NC(=O)CO3)O | ||||
| InChI | 1S/C21H26N2O4/c1-13-6-4-5-7-14(13)10-21(2,3)22-11-17(25)15-8-9-16(24)19-20(15)27-12-18(26)23-19/h4-9,17,22,24-25H,10-12H2,1-3H3,(H,23,26)/t17-/m0/s1 | ||||
| InChIKey | NWQXBEWHTDRJIP-KRWDZBQOSA-N | ||||
| PubChem Compound ID | 49837874 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 4LDE Structure of beta2 adrenoceptor bound to BI167107 and an engineered nanobody | ||||||
| Method | X-ray diffraction | Resolution | 2.79 Å | Mutation | Yes | [1] |
| PDB Sequence |
DAENLYFQGN
867 IFEMLRIDEG877 LRLKIYKDTE887 GYYTIGIGHL897 LTKSPSLNAA907 KSELDKAIGR 917 NTNGVITKDE927 AEKLFNQDVD937 AAVRGILRNA947 KLKPVYDSLD957 AVRRAALINM 967 VFQMGETGVA977 GFTNSLRMLQ987 QKRWDEAAVN997 LAKSRWYNQT1007 PNRAKRVITT 1017 FRTGTWDAYA1027 ADEVWVVGMG1037 IVMSLIVLAI1047 VFGNVLVITA1057 IAKFERLQTV 1067 TNYFITSLAC1077 ADLVMGLAVV1087 PFGAAHILTK1097 TWTFGNFWCE1107 FWTSIDVLCV 1117 TASIETLCVI1127 AVDRYFAITS1137 PFKYQSLLTK1147 NKARVIILMV1157 WIVSGLTSFL 1167 PIQMHWYRAT1177 HQEAINCYAE1187 ETCCDFFTNQ1197 AYAIASSIVS1207 FYVPLVIMVF 1217 VYSRVFQEAK1227 RQLQKFALKE1268 HKALKTLGII1278 MGTFTLCWLP1288 FFIVNIVHVI 1298 QDNLIRKEVY1308 ILLNWIGYVN1318 SGFNPLIYCR1328 SPDFRIAFQE1338 LLCL |
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|
|
HIS1093
4.656
TRP1109
3.368
THR1110
3.841
ASP1113
2.781
VAL1114
3.561
VAL1117
3.745
THR1118
4.503
CYS1191
3.446
ASP1192
4.209
PHE1193
3.418
THR1195
4.775
TYR1199
4.623
|
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| PDB ID: 6N48 Structure of beta2 adrenergic receptor bound to BI167107, Nanobody 6B9, and a positive allosteric modulator | ||||||
| Method | X-ray diffraction | Resolution | 3.20 Å | Mutation | Yes | [2] |
| PDB Sequence |
DAENLYFQGN
867 IFEMLRIDEG877 LRLKIYKDTE887 GYYTIGIGHL897 LTKSPSLNAA907 KSELDKAIGR 917 NTNGVITKDE927 AEKLFNQDVD937 AAVRGILRNA947 KLKPVYDSLD957 AVRRAALINM 967 VFQMGETGVA977 GFTNSLRMLQ987 QKRWDEAAVN997 LAKSRWYNQT1007 PNRAKRVITT 1017 FRTGTWDAYA1027 ADEVWVVGMG1037 IVMSLIVLAI1047 VFGNVLVITA1057 IAKFERLQTV 1067 TNYFITSLAC1077 ADLVMGLAVV1087 PFGAAHILTK1097 TWTFGNFWCE1107 FWTSIDVLCV 1117 TASIETLCVI1127 AVDRYFAITS1137 PFKYQSLLTK1147 NKARVIILMV1157 WIVSGLTSFL 1167 PIQMHWYRAT1177 HQEAINCYAE1187 ETCCDFFTNQ1197 AYAIASSIVS1207 FYVPLVIMVF 1217 VYSRVFQEAK1227 RQLQKFALKE1268 HKALKTLGII1278 MGTFTLCWLP1288 FFIVNIVHVI 1298 QDNLIRKEVY1308 ILLNWIGYVN1318 SGFNPLIYCR1328 SPDFRIAFQE1338 LLCL |
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|
HIS1093
4.831
TRP1109
3.667
THR1110
3.789
ASP1113
2.546
VAL1114
3.621
VAL1117
3.713
THR1118
4.054
CYS1191
3.666
ASP1192
4.431
PHE1193
3.376
THR1195
4.648
TYR1199
4.593
|
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| PDB ID: 3P0G Structure of a nanobody-stabilized active state of the beta2 adrenoceptor | ||||||
| Method | X-ray diffraction | Resolution | 3.50 Å | Mutation | Yes | [3] |
| PDB Sequence |
DVTQQRDEVW
32 VVGMGIVMSL42 IVLAIVFGNV52 LVITAIAKFE62 RLQTVTNYFI72 TSLACADLVM 82 GLAVVPFGAA92 HILMKMWTFG102 NFWCEFWTSI112 DVLCVTASIE122 TLCVIAVDRY 132 FAITSPFKYQ142 SLLTKNKARV152 IILMVWIVSG162 LTSFLPIQMH172 WYRATHQEAI 182 NCYAEETCCD192 FFTNQAYAIA202 SSIVSFYVPL212 VIMVFVYSRV222 FQEAKLKEHK 270 ALKTLGIIMG280 TFTLCWLPFF290 IVNIVHVIQD300 NLIRKEVYIL310 LNWIGYVNSG 320 FNPLIYCRSP330 DFRIAFQELL340 CLRR
|
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|
|
HIS93
4.316
TRP109
3.089
THR110
3.835
ASP113
2.730
VAL114
4.146
VAL117
3.533
THR118
4.907
CYS191
3.207
ASP192
3.847
PHE193
3.333
THR195
4.256
TYR199
4.485
ALA200
3.320
|
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| PDB ID: 6NI3 B2V2R-Gs protein subcomplex of a GPCR-G protein-beta-arrestin mega-complex | ||||||
| Method | Electron microscopy | Resolution | 3.80 Å | Mutation | No | [4] |
| PDB Sequence |
EVWVVGMGIV
39 MSLIVLAIVF49 GNVLVITAIA59 KFERLQTVTN69 YFITSLACAD79 LVMGLAVVPF 89 GAAHILTKTW99 TFGNFWCEFW109 TSIDVLCVTA119 SIETLCVIAV129 DRYFAITSPF 139 KYQSLLTKNK149 ARVIILMVWI159 VSGLTSFLPI169 QMHWYRQEAI182 NCYAEETCCD 192 FFTNQAYAIA202 SSIVSFYVPL212 VIMVFVYSRV222 FQEAKRQLQK232 IDKSEGRCLK 267 EHKALKTLGI277 IMGTFTLCWL287 PFFIVNIVHV297 IQDNLIRKEV307 YILLNWIGYV 317 NSGFNPLIYC327 RSPDFRIAFQ337 ELLC
|
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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .P0G or .P0G2 or .P0G3 or :3P0G;style chemicals stick;color identity;select .R:93 or .R:109 or .R:110 or .R:113 or .R:114 or .R:117 or .R:118 or .R:191 or .R:192 or .R:193 or .R:200 or .R:203 or .R:204 or .R:207 or .R:289 or .R:290 or .R:293 or .R:305 or .R:308 or .R:309 or .R:312 or .R:316; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
HIS93
3.432
TRP109
3.590
THR110
3.855
ASP113
2.482
VAL114
3.660
VAL117
3.678
THR118
4.337
CYS191
3.175
ASP192
4.402
PHE193
3.518
ALA200
4.330
|
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| PDB ID: 3SN6 Crystal structure of the beta2 adrenergic receptor-Gs protein complex | ||||||
| Method | X-ray diffraction | Resolution | 3.20 Å | Mutation | Yes | [5] |
| PDB Sequence |
NIFEMLRIDE
1011 GLRLKIYKDT1021 EGYYTIGIGH1031 LLTKSPSLNA1041 AKSELDKAIG1051 RNTNGVITKD 1061 EAEKLFNQDV1071 DAAVRGILRN1081 AKLKPVYDSL1091 DAVRRAALIN1101 MVFQMGETGV 1111 AGFTNSLRML1121 QQKRWDEAAV1131 NLAKSRWYNQ1141 TPNRAKRVIT1151 TFRTGTWDAE 30 VWVVGMGIVM40 SLIVLAIVFG50 NVLVITAIAK60 FERLQTVTNY70 FITSLACADL 80 VMGLAVVPFG90 AAHILTKTWT100 FGNFWCEFWT110 SIDVLCVTAS120 IETLCVIAVD 130 RYFAITSPFK140 YQSLLTKNKA150 RVIILMVWIV160 SGLTSFLPIQ170 MHWYRQEAIN 183 CYAEETCCDF193 FTNQAYAIAS203 SIVSFYVPLV213 IMVFVYSRVF223 QEAKRQLQKI 233 DKSEGRCLKE268 HKALKTLGII278 MGTFTLCWLP288 FFIVNIVHVI298 QDNLIRKEVY 308 ILLNWIGYVN318 SGFNPLIYCR328 SPDFRIAFQE338 LLC
|
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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .P0G or .P0G2 or .P0G3 or :3P0G;style chemicals stick;color identity;select .R:109 or .R:110 or .R:113 or .R:114 or .R:117 or .R:118 or .R:191 or .R:192 or .R:193 or .R:199 or .R:200 or .R:203 or .R:204 or .R:207 or .R:286 or .R:289 or .R:290 or .R:293 or .R:305 or .R:308 or .R:309 or .R:312 or .R:316; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
TRP109
3.323
THR110
3.619
ASP113
2.678
VAL114
3.932
VAL117
3.492
THR118
4.616
CYS191
4.093
ASP192
3.843
PHE193
3.126
TYR199
4.333
ALA200
3.706
SER203
2.816
|
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| PDB ID: 6E67 Structure of beta2 adrenergic receptor fused to a Gs peptide | ||||||
| Method | X-ray diffraction | Resolution | 3.70 Å | Mutation | Yes | [6] |
| PDB Sequence |
DEVWVVGMGI
38 VMSLIVLAIV48 FGNVLVITAI58 AKFERLQTVT68 NYFITSLACA78 DLVMGLAVVP 88 FGAAHILTKT98 WTFGNFWCEF108 WTSIDVLCVT118 ASIETLCVIA128 VDRYFAITSP 138 FKYQSLLTKN148 KARVIILMVW158 IVSGLTSFLP168 IQMHWYRATH178 QEAINCYAEE 188 TCCDFFTNQA198 YAIASSIVSF208 YVPLVIMVFV218 YSRVFQECKR228 QLQKNIFEML 1007 RIDEGLRLKI1017 YKDTEGYYTI1027 GIGHLLTKSP1037 SLNAAKSELD1047 KAIGRNTNGV 1057 ITKDEAEKLF1067 NQDVDAAVRG1077 ILRNAKLKPV1087 YDSLDAVRRA1097 ALINMVFQMG 1107 ETGVAGFTNS1117 LRMLQQKRWD1127 EAAVNLAKSR1137 WYNQTPNRAK1147 RVITTFRTGT 1157 WDAYDIIQRM2386 HLRQYELCGT3002 GEHKALKTLG276 IIMGTFTLCW286 LPFFIVNIVH 296 VIQDNLIRKE306 VYILLNWIGY316 VNSGFNPLIY326 CRSPDFRIAF336 QELLCLR |
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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .P0G or .P0G2 or .P0G3 or :3P0G;style chemicals stick;color identity;select .A:109 or .A:110 or .A:113 or .A:114 or .A:117 or .A:118 or .A:191 or .A:192 or .A:193 or .A:195 or .A:199 or .A:200 or .A:203 or .A:204 or .A:207 or .A:286 or .A:289 or .A:290 or .A:293 or .A:305 or .A:308 or .A:309 or .A:312 or .A:316; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
TRP109
3.398
THR110
3.619
ASP113
2.787
VAL114
3.525
VAL117
3.965
THR118
4.493
CYS191
4.478
ASP192
4.128
PHE193
3.394
THR195
4.870
TYR199
4.237
ALA200
3.468
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Adrenaline-activated structure of beta2-adrenoceptor stabilized by an engineered nanobody. Nature. 2013 Oct 24;502(7472):575-579. | ||||
| REF 2 | Mechanism of beta(2)AR regulation by an intracellular positive allosteric modulator. Science. 2019 Jun 28;364(6447):1283-1287. | ||||
| REF 3 | Structure of a nanobody-stabilized active state of the beta(2) adrenoceptor. Nature. 2011 Jan 13;469(7329):175-80. | ||||
| REF 4 | Structure of an endosomal signaling GPCR-G protein-beta-arrestin megacomplex. Nat Struct Mol Biol. 2019 Dec;26(12):1123-1131. | ||||
| REF 5 | Crystal structure of the beta2 adrenergic receptor-Gs protein complex. Nature. 2011 Jul 19;477(7366):549-55. | ||||
| REF 6 | Structural Insights into the Process of GPCR-G Protein Complex Formation. Cell. 2019 May 16;177(5):1243-1251.e12. | ||||
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