Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T11448 | Target Info | |||
| Target Name | Adrenergic receptor alpha-2A (ADRA2A) | ||||
| Synonyms | Alpha-2AAR; Alpha-2A adrenoreceptor; Alpha-2A adrenoceptor; Alpha-2A adrenergic receptor; Alpha-2 adrenergic receptor subtype C10; ADRAR; ADRA2R | ||||
| Target Type | Successful Target | ||||
| Gene Name | ADRA2A | ||||
| Biochemical Class | GPCR rhodopsin | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Brimonidine | Ligand Info | |||||
| Structure Description | Structure of the alpha2A-adrenergic receptor GoA signaling complex bound to brimonidine | PDB:7EJ8 | ||||
| Method | Electron microscopy | Resolution | 3.00 Å | Mutation | No | [1] |
| PDB Sequence |
YSLQVTLTLV
52 CLAGLLMLLT62 VFGNVLVIIA72 VFTSRALKAP82 QNLFLVSLAS92 ADILVATLVI 102 PFSLANEVMG112 YWYFGKAWCE122 IYLALDVLFC132 TSSIVHLCAI142 SLDRYWSITQ 152 AIEYNLKRTP162 RRIKAIIITV172 WVISAVISFP182 PRCEINDQKW210 YVISSCIGSF 220 FAPCLIMILV230 YVRIYQIAKR240 RTRRGRQNRE384 KRFTFVLAVV394 IGVFVVCWFP 404 FFFTYTLTAV414 GCSVPRTLFK424 FFFWFGYCNS434 SLNPVIYTIF444 NHDFRRAFKK 454 ILC
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| Ligand Name: Norepinephrine | Ligand Info | |||||
| Structure Description | Structure of the alpha2A-adrenergic receptor GoA signaling complex | PDB:7EJ0 | ||||
| Method | Electron microscopy | Resolution | 3.20 Å | Mutation | No | [1] |
| PDB Sequence |
QVTLTLVCLA
55 GLLMLLTVFG65 NVLVIIAVFT75 SRALKAPQNL85 FLVSLASADI95 LVATLVIPFS 105 LANEVMGYWY115 FGKAWCEIYL125 ALDVLFCTSS135 IVHLCAISLD145 RYWSITQAIE 155 YNLKRTPRRI165 KAIIITVWVI175 SAVISFPPLR202 CEINDQKWYV212 ISSCIGSFFA 222 PCLIMILVYV232 RIYQIAKRRT242 RGRQNREKRF387 TFVLAVVIGV397 FVVCWFPFFF 407 TYTLTAVGCS417 VPRTLFKFFF427 WFGYCNSSLN437 PVIYTIFNHD447 FRRAFKKILC 457
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| Ligand Name: Oxymetazoline | Ligand Info | |||||
| Structure Description | Structure of the alpha2A-adrenergic receptor GoA signaling complex bound to oxymetazoline | PDB:7EJK | ||||
| Method | Electron microscopy | Resolution | 3.40 Å | Mutation | No | [1] |
| PDB Sequence |
QVTLTLVCLA
55 GLLMLLTVFG65 NVLVIIAVFT75 SRALKAPQNL85 FLVSLASADI95 LVATLVIPFS 105 LANEVMGYWY115 FGKAWCEIYL125 ALDVLFCTSS135 IVHLCAISLD145 RYWSITQAIE 155 YNLKRTPRRI165 KAIIITVWVI175 SAVISFPPRC203 EINDQKWYVI213 SSCIGSFFAP 223 CLIMILVYVR233 IYQIAKRRTR243 QNREKRFTFV390 LAVVIGVFVV400 CWFPFFFTYT 410 LTAVGCSVPR420 TLFKFFFWFG430 YCNSSLNPVI440 YTIFNHDFRR450 AFKKILC |
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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 .J5C or .J5C2 or .J5C3 or :3J5C;style chemicals stick;color identity;select .R:128 or .R:129 or .R:132 or .R:133 or .R:211 or .R:212 or .R:215 or .R:216 or .R:402 or .R:405 or .R:409 or .R:427 or .R:431; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: Dexmedetomidine | Ligand Info | |||||
| Structure Description | Structure of the alpha2A-adrenergic receptor GoA signaling complex bound to dexmedetomidine | PDB:7EJA | ||||
| Method | Electron microscopy | Resolution | 3.60 Å | Mutation | No | [1] |
| PDB Sequence |
YSLQVTLTLV
52 CLAGLLMLLT62 VFGNVLVIIA72 VFTSRALKAP82 QNLFLVSLAS92 ADILVATLVI 102 PFSLANEVMG112 YWYFGKAWCE122 IYLALDVLFC132 TSSIVHLCAI142 SLDRYWSITQ 152 AIEYNLKRTP162 RRIKAIIITV172 WVISAVISFP182 PLEPRCEIND207 QKWYVISSCI 217 GSFFAPCLIM227 ILVYVRIYQI237 AKRRTRSRWR378 GRQNREKRFT388 FVLAVVIGVF 398 VVCWFPFFFT408 YTLTAVGCSV418 PRTLFKFFFW428 FGYCNSSLNP438 VIYTIFNHDF 448 RRAFKKILC
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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 .CZX or .CZX2 or .CZX3 or :3CZX;style chemicals stick;color identity;select .R:101 or .R:128 or .R:129 or .R:132 or .R:133 or .R:205 or .R:215 or .R:219 or .R:402 or .R:405 or .R:406 or .R:409 or .R:427 or .R:431; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Oleic acid | Ligand Info | |||||
| Structure Description | Crystal structures of the alpha2A adrenergic receptor in complex with an antagonist RSC. | PDB:6KUX | ||||
| Method | X-ray diffraction | Resolution | 2.70 Å | Mutation | No | [2] |
| PDB Sequence |
SLQVTLTLVC
38 LAGLLMLLTV48 FGNVLVIIAV58 FTSRALKAPQ68 NLFLVSLASA78 DILVATLVIP 88 FSLANEVMGY98 WYFGKAWCEI108 YLALDVLFCT118 SSAWHLCAIS128 LDRYWSITQA 138 IEYNLKRTPR148 RIKAIIITVW158 VISAVISFPP168 LISIEPAEPR187 CEINDQKWYV 197 ISSCIGSFFA207 PCLIMILVYV217 RIYQIAKRRT227 ADLEDNWETL1010 NDNLKVIEKA 1020 DNAAQVKDAL1030 TKMRAAALDA1040 QKATPPKLED1050 KSPDSPEMKD1060 FRHGFDILVG 1070 QIDDALKLAN1080 EGKVKEAQAA1090 AEQLKTTRNA1100 YIQKYLRQNR368 EKRFTFVLAV 378 VIGVFVVCWF388 PFFFTYTLTA398 VGCSVPRTLF408 KFFFWFGYCN418 SSLNPVIYTI 428 FNHDFRRAFK438 KILCR
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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 .OLA or .OLA2 or .OLA3 or :3OLA;style chemicals stick;color identity;select .A:133 or .A:137 or .A:141 or .A:144; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 5-(3-Bicyclo[4.2.0]octa-1,3,5-trienyl)-1,2,3,6-tetrahydropyridine | Ligand Info | |||||
| Structure Description | Cryo-EM structure of the alpha2A adrenergic receptor GoA signaling complex bound to a biased agonist | PDB:7W7E | ||||
| Method | Electron microscopy | Resolution | 3.40 Å | Mutation | No | [3] |
| PDB Sequence |
LQVTLTLVCL
54 AGLLMLLTVF64 GNVLVIIAVF74 TSRALKAPQN84 LFLVSLASAD94 ILVATLVIPF 104 SLANEVMGYW114 YFGKAWCEIY124 LALDVLFCTS134 SIVHLCAISL144 DRYWSITQAI 154 EYNLKRTPRR164 IKAIIITVWV174 ISAVISFPPR202 CEINDQKWYV212 ISSCIGSFFA 222 PCLIMILVYV232 RIYQIAKRRT242 RGRQNREKRF387 TFVLAVVIGV397 FVVCWFPFFF 407 TYTLTAVGCS417 VPRTLFKFFF427 WFGYCNSSLN437 PVIYTIFNHD447 FRRAFKKILC 457
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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 .W58 or .W582 or .W583 or :3W58;style chemicals stick;color identity;select .R:128 or .R:129 or .R:132 or .R:133 or .R:205 or .R:211 or .R:215 or .R:216 or .R:219 or .R:402 or .R:405 or .R:406 or .R:409 or .R:427 or .R:431; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: N-pyridin-4-ylisoquinolin-4-amine | Ligand Info | |||||
| Structure Description | Cryo-EM structure of the alpha2A adrenergic receptor GoA signaling complex bound to a G protein biased agonist | PDB:7W6P | ||||
| Method | Electron microscopy | Resolution | 3.47 Å | Mutation | No | [3] |
| PDB Sequence |
QVTLTLVCLA
55 GLLMLLTVFG65 NVLVIIAVFT75 SRALKAPQNL85 FLVSLASADI95 LVATLVIPFS 105 LANEVMGYWY115 FGKAWCEIYL125 ALDVLFCTSS135 IVHLCAISLD145 RYWSITQAIE 155 YNLKRTPRRI165 KAIIITVWVI175 SAVISFPPRC203 EINDQKWYVI213 SSCIGSFFAP 223 CLIMILVYVR233 IYQIAKRRTG379 RQNREKRFTF389 VLAVVIGVFV399 VCWFPFFFTY 409 TLTAVGCSVP419 RTLFKFFFWF429 GYCNSSLNPV439 IYTIFNHDFR449 RAFKKILC |
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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 .W96 or .W962 or .W963 or :3W96;style chemicals stick;color identity;select .R:128 or .R:129 or .R:132 or .R:133 or .R:205 or .R:215 or .R:219 or .R:402 or .R:405 or .R:406 or .R:409 or .R:427 or .R:428 or .R:430 or .R:431; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: (8aR,12aS,13aS)-12-ethylsulfonyl-3-methoxy-5,6,8,8a,9,10,11,12a,13,13a-decahydroisoquinolino[2,1-g][1,6]naphthyridine | Ligand Info | |||||
| Structure Description | Crystal structures of the alpha2A adrenergic receptor in complex with an antagonist RSC. | PDB:6KUX | ||||
| Method | X-ray diffraction | Resolution | 2.70 Å | Mutation | No | [2] |
| PDB Sequence |
SLQVTLTLVC
38 LAGLLMLLTV48 FGNVLVIIAV58 FTSRALKAPQ68 NLFLVSLASA78 DILVATLVIP 88 FSLANEVMGY98 WYFGKAWCEI108 YLALDVLFCT118 SSAWHLCAIS128 LDRYWSITQA 138 IEYNLKRTPR148 RIKAIIITVW158 VISAVISFPP168 LISIEPAEPR187 CEINDQKWYV 197 ISSCIGSFFA207 PCLIMILVYV217 RIYQIAKRRT227 ADLEDNWETL1010 NDNLKVIEKA 1020 DNAAQVKDAL1030 TKMRAAALDA1040 QKATPPKLED1050 KSPDSPEMKD1060 FRHGFDILVG 1070 QIDDALKLAN1080 EGKVKEAQAA1090 AEQLKTTRNA1100 YIQKYLRQNR368 EKRFTFVLAV 378 VIGVFVVCWF388 PFFFTYTLTA398 VGCSVPRTLF408 KFFFWFGYCN418 SSLNPVIYTI 428 FNHDFRRAFK438 KILCR
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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 .E3F or .E3F2 or .E3F3 or :3E3F;style chemicals stick;color identity;select .A:90 or .A:109 or .A:113 or .A:114 or .A:117 or .A:118 or .A:188 or .A:189 or .A:190 or .A:200 or .A:204 or .A:387 or .A:390 or .A:391 or .A:394 or .A:408 or .A:412 or .A:416; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: (2~{S})-4-fluoranyl-2-(1~{H}-imidazol-5-yl)-1-propan-2-yl-2,3-dihydroindole | Ligand Info | |||||
| Structure Description | Crystal structure of the alpha2A adrenergic receptor in complex with a partial agonist | PDB:6KUY | ||||
| Method | X-ray diffraction | Resolution | 3.20 Å | Mutation | No | [4] |
| PDB Sequence |
TLTLVCLAGL
42 LMLLTVFGNV52 LVIIAVFTSR62 ALKAPQNLFL72 VSLASADILV82 ATLVIPFSLA 92 NEVMGYWYFG102 KAWCEIYLAL112 DVLFCTSSAW122 HLCAISLDRY132 WSITQAIEYN 142 LKRTPRRIKA152 IILTVWVISA162 VISFPPLISI172 PAEPRCEIND192 QKWYVISSCI 202 GSFFAPCLIM212 ILVYVRIYQI222 AKRRTADLED1005 NWETLNDNLK1015 VIEKADNAAQ 1025 VKDALTKMRA1035 AALDAQKATP1045 PKLEDKSPDS1055 PEMKDFRHGF1065 DILVGQIDDA 1075 LKLANEGKVK1085 EAQAAAEQLK1095 TTRNAYIQKY1105 LRQNREKRFT373 FVLAVVIGVF 383 VVCWFPFFFT393 YTLTAVGCSV403 PRTLFKFFFW413 FGYCNSSLNP423 VIYTIFNHDF 433 RRAFKKILCR443
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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 .E39 or .E392 or .E393 or :3E39;style chemicals stick;color identity;select .A:113 or .A:114 or .A:116 or .A:117 or .A:118 or .A:190 or .A:200 or .A:204 or .A:205 or .A:387 or .A:390 or .A:391 or .A:394 or .A:412 or .A:416; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Structural insights into ligand recognition, activation, and signaling of the Alpha(2A) adrenergic receptor. Sci Adv. 2022 Mar 4;8(9):eabj5347. | ||||
| REF 2 | Crystal structures of the alpha2A adrenergic receptor in complex with an antagonist RSC. | ||||
| REF 3 | Structure-based discovery of nonopioid analgesics acting through the Alpha(2A)-adrenergic receptor. Science. 2022 Sep 30;377(6614):eabn7065. | ||||
| REF 4 | Crystal structures of the alpha2A adrenergic receptor in complex with a partial agonist | ||||
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