TABLE 4.
Reported structures of adenosine receptor subtypes
| PDB | Engineering | Ligand | Resolution (Å) | Technique | Remarks | Reference |
|---|---|---|---|---|---|---|
| A2AAR Antagonist Structures | ||||||
| 3PWH | TS | ZM241385 (42) | 3.3 | X-ray | (Dore et al., 2011) | |
| 3REY | TS | XAC (57) | 3.3 | X-ray | (Dore et al., 2011) | |
| 3RFM | TS | Caffeine (3) | 3.6 | X-ray | (Dore et al., 2011) | |
| 3UZA | TS | T4G (58) | 3.3 | X-ray | T4G: 6-(2,6-dimethylpyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine | (Congreve et al., 2012) |
| 3UZC | TS | T4E (59) | 3.3 | X-ray | T4E: 4-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-2-chlorophenol | (Congreve et al., 2012) |
| 3EML | FP (T4L) | ZM241385 | 2.6 | X-ray | (Jaakola et al., 2008) | |
| 4EIY | FP (bRIL) | ZM241385 | 1.8 | X-ray | (Liu et al., 2012) | |
| 5UIG | FP (bRIL) | 8D1 (60) | 3.5 | X-ray | 8D1: 5-amino-N-[(2-methoxyphenyl)methyl]-2-(3-methylphenyl)-2H-1,2,3-triazole-4-carboximidamide | (Sun et al., 2017) |
| 5K2A | FP (bRIL) | ZM241385 | 2.5 | X-ray/SFX/XFEL, sulfur SAD phasing | SFX: serial femtosecond crystallography; XFEL: X-ray free-electron laser; SAD: single-wavelength anomalous diffraction | (Batyuk et al., 2016) |
| 5K2B | FP (bRIL) | ZM241385 | 2.5 | X-ray/SFX/XFEL, MR phasing | MR: molecular replacement | (Batyuk et al., 2016) |
| 5K2C | FP (bRIL) | ZM241385 | 1.9 | X-ray/SFX/XFEL, sulfur SAD phasing and phase extension | (Batyuk et al., 2016) | |
| 5K2D | FP (bRIL) | ZM241385 | 1.9 | X-ray/SFX/XFEL, MR phasing | (Batyuk et al., 2016) | |
| 5VRA | FP (bRIL) | ZM241385 | 2.4 | X-ray in situ | in situ: film sandwich plates at room temperature | (Broecker et al., 2018) |
| 5JTB | FP (bRIL) | ZM241385 | 2.8 | X-ray/I-SAD | I-SAD: iodide-single-wavelength anomalous diffraction | (Melnikov et al., 2017) |
| 5UVI | FP (bRIL) | ZM241385 | 3.2 | X-ray millisec | millisec: serial millisecond crystallography using synchrotron radiation | (Martin-Garcia et al., 2017) |
| 6AQF | FP (bRIL) | ZM241385 | 2.5 | X-ray | (Eddy et al., 2018b) | |
| 7RM5 | FP (bRIL) | ZM241385 | 2.8 | Microcrystal electron diffraction | (Martynowycz et al., 2021) | |
| 5NM2 | TS-FP (bRIL) | ZM241385 | 2.0 | X-ray millisec (cryo) | (Weinert et al., 2017) | |
| 5NLX | TS-FP (bRIL) | ZM241385 | 2.1 | X-ray millisec (room temp) | (Weinert et al., 2017) | |
| 5NM4 | TS-FP (bRIL) | ZM241385 | 1.7 | X-ray femtosec (room temp) | Serial femtosecond crystallography using XFEL | (Weinert et al., 2017) |
| 5MZJ | TS-FP (bRIL) | Theophylline (4) | 2.0 | X-ray | (Cheng et al., 2017) | |
| 5MZP | TS-FP (bRIL) | Caffeine (3) | 2.1 | X-ray | (Cheng et al., 2017) | |
| 5N2R | TS-FP (bRIL) | PSB-36 (18) | 2.8 | X-ray | (Cheng et al., 2017) | |
| 5IU4 | TS-FP (bRIL) | ZM241385 | 1.7 | X-ray | (Segala et al., 2016) | |
| 5IU7 | TS-FP (bRIL) | 12c (61, LUF6805) | 1.9 | X-ray | 12c: 2-(furan-2-yl)-N5-(2-(4-phenylpiperidin-1-yl)ethyl)[1,2,4]triazolo[1,5-a][1,3,5]triazine-5,7-diamine | (Segala et al., 2016) |
| 5IU8 | TS-FP (bRIL) | 12f (62, LUF6806) | 2.0 | X-ray | 12f: 2-(furan-2-yl)-N5-(2-(4-methylpiperazin-1-yl)ethyl)[1,2,4]triazolo[1,5-a][1,3,5]triazine-5,7-diamine | (Segala et al., 2016) |
| 5IUA | TS-FP (bRIL) | 12b (63, LUF6732) | 2.2 | X-ray | 12b: 2-(furan-2-yl)-N5-(3-(4-phenylpiperazin-1-yl)propyl)[1,2,4]triazolo[1,5-a][1,3,5]triazine-5,7-diamine | (Segala et al., 2016) |
| 5IUB | TS-FP (bRIL) | 12x (64, LUF6632) | 2.1 | X-ray | 12x: N5-(2-(4-(2,4-difluorophenyl)piperazin-1-yl)ethyl)-2-(furan2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazine-5,7-diamine | (Segala et al., 2016) |
| 5OLG | TS-FP (bRIL) | ZM241385 | 1.9 | X-ray, soaking | soaking of ligand to displace theophylline in the crystals | (Rucktooa et al., 2018) |
| 5OLH | TS-FP (bRIL) | Vipadenant (65) | 2.6 | X-ray, soaking for 24 hr | (Rucktooa et al., 2018) | |
| 5OLO | TS-FP (bRIL) | Tozadenant (66) | 3.1 | X-ray, soaking for 24 hr | (Rucktooa et al., 2018) | |
| 5OLV | TS-FP (bRIL) | LUAA47070 (analog) (67/68) | 2.0 | X-ray, soaking for 24 hr | (Rucktooa et al., 2018) | |
| 5OLZ | TS-FP (bRIL) | 4e (69) | 1.9 | X-ray | 4e: 4-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-2-chlorophenol | (Rucktooa et al., 2018) |
| 5OM1 | TS-FP (bRIL) | 4e | 2.1 | X-ray, soaking for 1 hr | (Rucktooa et al., 2018) | |
| 5OM4 | TS-FP (bRIL) | 4e | 2.0 | X-ray, soaking for 24 hr | (Rucktooa et al., 2018) | |
| 6LPJ/K/L | FP (bRIL) | ZM241385 | 1.8–2.0 | Serial femtosecond crystallography using XFEL | EROCOC17 + 4 as crystallization matrix | (Ihara et al., 2020) |
| 6ZDR | TS-FP (bRIL) | Chromone 4d (70) | 1.9 | X-ray | (Jespers et al., 2020) | |
| 6ZDV | TS-FP (bRIL) | Chromone 5d (71) | 2.1 | X-ray | (Jespers et al., 2020) | |
| 6GT3 | TS-FP (bRIL) | AZD4635 (22) | 2.0 | X-ray | (Borodovsky et al., 2020) | |
| 6S0Q | TS-FP (bRIL) | ZM241385 | 2.7 | Native SAD | SAD: single-wavelength anomalous diffraction | (Nass et al., 2020) |
| 3VG9 | antibody-stab | ZM241385 | 2.7 | X-ray | (Hino et al., 2012) | |
| 3VGA | antibody-stab | ZM241385 | 3.1 | X-ray | (Hino et al., 2012) | |
| A2AAR Agonist Structures | ||||||
| 2YDO | TS | Adenosine (1) | 3.0 | X-ray | (Lebon et al., 2011) | |
| 2YDV | TS | NECA (6) | 2.6 | X-ray | (Lebon et al., 2011) | |
| 4UG2 | TS | CGS21680 (10) | 2.6 | X-ray | (Lebon et al., 2015) | |
| 4UHR | TS | CGS21680 | 2.6 | X-ray | (Lebon et al., 2015) | |
| 3QAK | FP (T4L) | UK432097 (11) | 2.7 | X-ray | WT receptor | (Xu et al., 2011) |
| 5WF5 | FP (bRIL) | UK432097 | 2.6 | X-ray | D52N mutant | (White et al., 2018) |
| 5WF6 | FP (bRIL) | UK432097 | 2.9 | X-ray | S91A mutant | (White et al., 2018) |
| 5G53 | truncated and tagged WT | NECA (6) | 3.4 | X-ray | with engineered G protein (mini-Gs) | (Carpenter et al., 2016) |
| 6GDG | FP (thioredoxin) | NECA | 4.1 | cryo-EM | with engineered G protein (mini-Gs-β1γ2); also includes nanobody Nb35 | (Garcia-Nafria et al., 2018) |
| 7ARO | TS-FP (bRIL) | LUF5833 (56) | 3.1 | X-ray | LUF5833 is a partial agonist | (Amelia et al., 2021) |
| A1AR Antagonist Structures | ||||||
| 5N2S | TS | PSB-36 (18) | 3.3 | X-ray | (Cheng et al., 2017) | |
| 5UEN | FP (bRIL) | DU172 (72) | 3.2 | X-ray | (Glukhova et al., 2017) | |
| A1AR Agonist Structures | ||||||
| 6D9H | tagged WT receptor | Adenosine (1) | 3.6 | cryo-EM | with engineered Gi2 protein | (Draper-Joyce et al., 2018) |
| 7LD3/4 | tagged WT receptor | Adenosine (1) +/− MIPS521 (73) | 3.3–3.4 | cryo-EM | with engineered Gi2 protein | (Draper-Joyce et al., 2021) |